Brain Imaging & Neurogenetics Lab
Led by Principal Investigator Robyn Honea, PhD,
the lab has combined advanced neuroimaging techniques with genetic analyses to advance brain health.
Our Research
The lab has combined advanced neuroimaging techniques with genetic analyses to uncover the biological underpinnings of Alzheimer’s disease and advance brain health. Dr. Honea’s work has investigated how genes, particularly APOE and TOMM40, may modulate brain structure and function, and has applied imaging biomarkers to evaluate the impact of lifestyle interventions, such as exercise and diet, on neurodegenerative processes. Her research has been particularly interested in the interplay between the environment, mitochondrial genes, nuclear genes, and the aging process. The lab has also provided robust mentoring for trainees at all levels, from undergraduate interns to junior faculty, helping foster the next generation of neuroimaging researchers.
MRI
T1 structural, FLAIR, high‑res hippocampal, ASL perfusion, QSM/SWI, DTI white‑matter, resting‑state & task fMRI including volumes, thickness, sulcal depth, gyrification index, fractal dimension, white matter lesion, tract-based diffusion measures, cerebral blood flow SUVR, hippocampal subregion volumes, and microhemorrhage information.
PET
Amyloid (Florbetaben/Florbetapir), Tau, FDG‑glucose, including SUVR and centiloid data.
Neurogenetics
Imaging-linked genetic data and omics analysis support.
Data Analytics
Integrated data management, analysis pipelines, imaging-centric machine learning, statistical support, and training for investigators.
The laboratory has been based at the University of Kansas School of Medicine. Dr. Honea has served as Director of the Neuroimaging Core of the University of Kansas Alzheimer’s Disease Research Center (KU ADRC) and as an Associate Professor in the Department of Neurology. Through the integration of state-of-the-art MRI, PET, and genetics resources, the lab has supported center-wide studies of aging and dementia and contributed to collaborative projects using advanced neuroimaging tools.
Selected Publications
Honea, Robyn A; Watts, Amber; Donofry, Shannon D; Molina-Hidalgo, Cristina; Ripperger, Hayley S; Aghjayan, Sarah L; Kang, Chaeryon; Gujral, Swathi; Oberlin, Lauren E; Grove, George; Huang, Haiqing; Sutton, Bradley P; Burns, Jeffrey M; Vidoni, Eric D; Kramer, Arthur F; McAuley, Edward; Hillman, Charles H; Marsland, Anna L; Kamboh, M Ilyas; Erickson, Kirk I
Lifespan exposure to hormone therapies and structural brain morphometry in older women Journal Article
In: Neuroimage, vol. 334, pp. 121974, 2026, ISSN: 1095-9572.
@article{pmid42082089,
title = {Lifespan exposure to hormone therapies and structural brain morphometry in older women},
author = {Robyn A Honea and Amber Watts and Shannon D Donofry and Cristina Molina-Hidalgo and Hayley S Ripperger and Sarah L Aghjayan and Chaeryon Kang and Swathi Gujral and Lauren E Oberlin and George Grove and Haiqing Huang and Bradley P Sutton and Jeffrey M Burns and Eric D Vidoni and Arthur F Kramer and Edward McAuley and Charles H Hillman and Anna L Marsland and M Ilyas Kamboh and Kirk I Erickson},
doi = {10.1016/j.neuroimage.2026.121974},
issn = {1095-9572},
year = {2026},
date = {2026-07-01},
journal = {Neuroimage},
volume = {334},
pages = {121974},
abstract = {BACKGROUND: Although many studies support a neuroprotective role for estrogens and other ovarian hormones in women, findings across imaging studies remain mixed. Few studies have explored both early- and midlife- hormone exposures simultaneously or incorporated whole-brain, voxel-wise approaches. This study examined the effects of early- and midlife exposure to ovarian hormones- via hormonal birth control (BC), menopausal hormone therapy (MHT)- and their timing on brain health in older women. We also studied the relationship of age of menopause (i.e., greater endogenous exposure to ovarian hormones) to brain health in older adulthood.nnMETHODS: We analyzed baseline data from 459 women (ages 65-80) in the multi-site IGNITE study, a 12-month randomized aerobic exercise study. We examined retrospective self-report of BC and MHT use in relation to structural MRI metrics using voxel-based morphometry (VBM) for gray matter volume and surface-based morphometry (SBM) for cortical thickness.nnFINDINGS: BC use compared to no BC use was associated with greater gray matter volume in temporal, occipital, and frontal regions in older adulthood. Longer BC duration was linked to larger fusiform gyrus volume. Combined BC and MHT use compared to no use was associated with greater volume in parietal and temporal areas and thicker cortex in the posterior cingulate and temporal gyri. Later menopause onset correlated with greater posterior cortical thickness. No associations were found for MHT timing or BC start age.nnINTERPRETATIONS: Both endogenous and exogenous lifetime exposure to ovarian hormones were associated with structural brain measures generally consistent with preserved brain aging. These findings highlight the importance of exposure timing in women's brain health and AD risk prevention.},
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BACKGROUND: Although many studies support a neuroprotective role for estrogens and other ovarian hormones in women, findings across imaging studies remain mixed. Few studies have explored both early- and midlife- hormone exposures simultaneously or incorporated whole-brain, voxel-wise approaches. This study examined the effects of early- and midlife exposure to ovarian hormones- via hormonal birth control (BC), menopausal hormone therapy (MHT)- and their timing on brain health in older women. We also studied the relationship of age of menopause (i.e., greater endogenous exposure to ovarian hormones) to brain health in older adulthood.nnMETHODS: We analyzed baseline data from 459 women (ages 65-80) in the multi-site IGNITE study, a 12-month randomized aerobic exercise study. We examined retrospective self-report of BC and MHT use in relation to structural MRI metrics using voxel-based morphometry (VBM) for gray matter volume and surface-based morphometry (SBM) for cortical thickness.nnFINDINGS: BC use compared to no BC use was associated with greater gray matter volume in temporal, occipital, and frontal regions in older adulthood. Longer BC duration was linked to larger fusiform gyrus volume. Combined BC and MHT use compared to no use was associated with greater volume in parietal and temporal areas and thicker cortex in the posterior cingulate and temporal gyri. Later menopause onset correlated with greater posterior cortical thickness. No associations were found for MHT timing or BC start age.nnINTERPRETATIONS: Both endogenous and exogenous lifetime exposure to ovarian hormones were associated with structural brain measures generally consistent with preserved brain aging. These findings highlight the importance of exposure timing in women's brain health and AD risk prevention.
Vidoni, Eric D; Mahnken, Jonathan D; Morris, Jill K; Wilkins, Heather M; Almaghraby, Abdulaziz; Honea, Robyn A; Billinger, Sandra A; Brunette, Amanda; Parks, Adam; Perales-Puchalt, Jaime; Hunt, Suzanne L; Baker, Jordan; Arthur, Anne K; Fikru, Samantha A; Cox, Keri; Burns, Jeffrey M; Townley, Ryan A
Operationalizing AD Biomarker Return of Research Results: Methods from the KU ADRC Journal Article
In: Biopreserv Biobank, pp. 19475535261447837, 2026, ISSN: 1947-5543.
@article{pmid42178834,
title = {Operationalizing AD Biomarker Return of Research Results: Methods from the KU ADRC},
author = {Eric D Vidoni and Jonathan D Mahnken and Jill K Morris and Heather M Wilkins and Abdulaziz Almaghraby and Robyn A Honea and Sandra A Billinger and Amanda Brunette and Adam Parks and Jaime Perales-Puchalt and Suzanne L Hunt and Jordan Baker and Anne K Arthur and Samantha A Fikru and Keri Cox and Jeffrey M Burns and Ryan A Townley},
doi = {10.1177/19475535261447837},
issn = {1947-5543},
year = {2026},
date = {2026-05-01},
journal = {Biopreserv Biobank},
pages = {19475535261447837},
abstract = {INTRODUCTION: Widespread implementation of Alzheimer's disease (AD) biomarkers in research settings introduces new opportunities and challenges for managing and returning complex, multi-modal testing results to research participants.nnOBJECTIVES: To describe a structured, participant-centered biomarker data management and return of results workflow developed at a U.S. Alzheimer's Disease Research Center (ADRC), and to provide preliminary data on participant and clinician experience with return of results.nnMETHODS: We developed an automated, interdisciplinary workflow to integrate multimodal biomarker data (neuroimaging, fluid, and genetics) into research consensus diagnostic conferences and individualized participant Return of Results reports. To evaluate feasibility and participant experience, we conducted a non-randomized study in which participants receiving biomarker results rated anxiety, depression, and decision regret within one week and at 3-month follow-up.nnRESULTS: The workflow was implemented using non-proprietary tools, with semi-automated data aggregation and nightly updates. Survey data indicated statistically significant changes in anxiety and depression following biomarker return of results, though the clinical relevance of these changes remains unclear, highlighting opportunities to improve utility.nnCONCLUSIONS: Using and returning biomarker results is feasible, scalable, and well-tolerated within a research setting. This model may guide broader adoption of AD biomarker management and return of results to participants in future study designs.},
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INTRODUCTION: Widespread implementation of Alzheimer's disease (AD) biomarkers in research settings introduces new opportunities and challenges for managing and returning complex, multi-modal testing results to research participants.nnOBJECTIVES: To describe a structured, participant-centered biomarker data management and return of results workflow developed at a U.S. Alzheimer's Disease Research Center (ADRC), and to provide preliminary data on participant and clinician experience with return of results.nnMETHODS: We developed an automated, interdisciplinary workflow to integrate multimodal biomarker data (neuroimaging, fluid, and genetics) into research consensus diagnostic conferences and individualized participant Return of Results reports. To evaluate feasibility and participant experience, we conducted a non-randomized study in which participants receiving biomarker results rated anxiety, depression, and decision regret within one week and at 3-month follow-up.nnRESULTS: The workflow was implemented using non-proprietary tools, with semi-automated data aggregation and nightly updates. Survey data indicated statistically significant changes in anxiety and depression following biomarker return of results, though the clinical relevance of these changes remains unclear, highlighting opportunities to improve utility.nnCONCLUSIONS: Using and returning biomarker results is feasible, scalable, and well-tolerated within a research setting. This model may guide broader adoption of AD biomarker management and return of results to participants in future study designs.
Patel, Ankit; Guiler, William; Pepper, Sam; Kemna, Riley E; Kueck, Paul J; Weidling, Ian W; Mayfield, Hana D; John, Casey S; Mudaranthakam, Dinesh Pal; Wilkins, Heather M; Swerdlow, Russell H; Burns, Jeffrey M; Morris, Jill K; Honea, Robyn A
Limbic-predominant neuroimaging correlates of plasma p-Tau217 in preclinical and clinical Alzheimer's disease Journal Article
In: Front Aging Neurosci, vol. 18, pp. 1748524, 2026, ISSN: 1663-4365.
@article{pmid42100483,
title = {Limbic-predominant neuroimaging correlates of plasma p-Tau217 in preclinical and clinical Alzheimer's disease},
author = {Ankit Patel and William Guiler and Sam Pepper and Riley E Kemna and Paul J Kueck and Ian W Weidling and Hana D Mayfield and Casey S John and Dinesh Pal Mudaranthakam and Heather M Wilkins and Russell H Swerdlow and Jeffrey M Burns and Jill K Morris and Robyn A Honea},
doi = {10.3389/fnagi.2026.1748524},
issn = {1663-4365},
year = {2026},
date = {2026-01-01},
journal = {Front Aging Neurosci},
volume = {18},
pages = {1748524},
abstract = {BACKGROUND: Plasma phosphorylated tau at threonine 217 (p-Tau217) has emerged as a highly sensitive and specific blood-based biomarker for Alzheimer's Disease (AD). However, its regional brain correlates with multimodal neuroimaging, beyond tau-PET, remain underexplored, particularly in early disease phases where limbic involvement may predominate. This study aimed to map the associations of plasma p-Tau217 with amyloid-PET burden, FDG-PET metabolism, and structural brain morphometry in a well-characterized cohort spanning cognitively unimpaired (CU) and cognitively impaired (CI) individuals across AD dementia stages, hypothesizing increased AD neuroimaging biomarkers in individuals with elevated p-Tau217.nnMETHODS: We analyzed data from 259 participants from the University of Kansas Alzheimer's Disease Research Center (KU ADRC) Clinical Cohort. Imaging outcomes included amyloid-PET, FDG-PET, gray matter volumetric regions of interest as well as whole brain voxel-based morphometry (VBM), and surface-based morphometry (SBM) for cortical thickness (CT), sulcal depth (SD), gyrification index (GI), fractal dimension (FD). Analyses were stratified by diagnostic and pTau-217 positivity (CU pTau + , CU pTau -, CI pTau + and CI pTau-). Spearman's correlations and voxel/surface-wise regressions evaluated p-Tau217 associations with imaging metrics, accounting for age and sex.nnRESULTS: Plasma p-Tau217 was elevated in CI versus CU. Individuals with elevated plasma p-Tau217 had increased amyloid-PET deposition across the cortex, as well as significantly higher centiloids, both in CU and CI individuals. In CI individuals, elevated p-Tau217 was associated with reduced voxel-wise gray matter volume and cortical thickness in limbic, temporal, parietal, and frontal regions, plus increased cingulate FD. In both CU and CI pTau + individuals, p-Tau217 correlated with AD Signature gray matter decreases.nnCONCLUSION: These findings show that CU and CI individuals with elevated plasma p-Tau217 have both increased amyloid-PET burden but also temporolimbic gray matter atrophy and hypometabolism. This supports p-Tau217 as a minimally invasive, scalable biomarker for early AD detection, risk stratification, and prognostic monitoring in preclinical stages, potentially guiding trial enrichment and personalized interventions.},
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pubstate = {published},
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BACKGROUND: Plasma phosphorylated tau at threonine 217 (p-Tau217) has emerged as a highly sensitive and specific blood-based biomarker for Alzheimer's Disease (AD). However, its regional brain correlates with multimodal neuroimaging, beyond tau-PET, remain underexplored, particularly in early disease phases where limbic involvement may predominate. This study aimed to map the associations of plasma p-Tau217 with amyloid-PET burden, FDG-PET metabolism, and structural brain morphometry in a well-characterized cohort spanning cognitively unimpaired (CU) and cognitively impaired (CI) individuals across AD dementia stages, hypothesizing increased AD neuroimaging biomarkers in individuals with elevated p-Tau217.nnMETHODS: We analyzed data from 259 participants from the University of Kansas Alzheimer's Disease Research Center (KU ADRC) Clinical Cohort. Imaging outcomes included amyloid-PET, FDG-PET, gray matter volumetric regions of interest as well as whole brain voxel-based morphometry (VBM), and surface-based morphometry (SBM) for cortical thickness (CT), sulcal depth (SD), gyrification index (GI), fractal dimension (FD). Analyses were stratified by diagnostic and pTau-217 positivity (CU pTau + , CU pTau -, CI pTau + and CI pTau-). Spearman's correlations and voxel/surface-wise regressions evaluated p-Tau217 associations with imaging metrics, accounting for age and sex.nnRESULTS: Plasma p-Tau217 was elevated in CI versus CU. Individuals with elevated plasma p-Tau217 had increased amyloid-PET deposition across the cortex, as well as significantly higher centiloids, both in CU and CI individuals. In CI individuals, elevated p-Tau217 was associated with reduced voxel-wise gray matter volume and cortical thickness in limbic, temporal, parietal, and frontal regions, plus increased cingulate FD. In both CU and CI pTau + individuals, p-Tau217 correlated with AD Signature gray matter decreases.nnCONCLUSION: These findings show that CU and CI individuals with elevated plasma p-Tau217 have both increased amyloid-PET burden but also temporolimbic gray matter atrophy and hypometabolism. This supports p-Tau217 as a minimally invasive, scalable biomarker for early AD detection, risk stratification, and prognostic monitoring in preclinical stages, potentially guiding trial enrichment and personalized interventions.
Geiger, Paige C; Pennington, Jenae S; Kueck, Paul J; John, Casey S; Mayfield, Hana D; Kemna, Riley E; Burns, Jeffrey; Vidoni, Eric; Honea, Robyn; Li, Yanming; Mahnken, Jonathan; Morris, Jill K
Heat therapy in individuals at risk for Alzheimer's disease-methods for a randomized controlled trial Journal Article
In: Front Neurol, vol. 17, pp. 1736108, 2026, ISSN: 1664-2295.
@article{pmid41657418,
title = {Heat therapy in individuals at risk for Alzheimer's disease-methods for a randomized controlled trial},
author = {Paige C Geiger and Jenae S Pennington and Paul J Kueck and Casey S John and Hana D Mayfield and Riley E Kemna and Jeffrey Burns and Eric Vidoni and Robyn Honea and Yanming Li and Jonathan Mahnken and Jill K Morris},
doi = {10.3389/fneur.2026.1736108},
issn = {1664-2295},
year = {2026},
date = {2026-01-01},
journal = {Front Neurol},
volume = {17},
pages = {1736108},
abstract = {Heat therapy (HT) has been shown to improve peripheral blood glucose regulation in some populations, yet its effects on brain glucose metabolism remain largely unexplored. The chronic benefits of HT may arise in part from upregulation of heat-shock proteins (HSPs). These proteins play a crucial role in the stress response and modulate diverse processes such as proteostasis and cell signaling pathways, including that of insulin signaling. Understanding the impact of HT on both peripheral and central glucose metabolism, including the effects of varying temperatures, is essential for elucidating potential mechanisms underlying its brain benefits. The Feasibility of Improving Glycemia to prevent Alzheimer's Disease (FIGHT-AD) study is a randomized controlled trial that aims to investigate changes in blood and brain glucose regulation following 10 weeks of HT. Specifically, we will examine the peripheral biomarker responses to warm and hot HT and assess how these responses relate to brain metabolic changes in both treatment groups. This trial will be the first to quantify the effect of HT on cerebral glucose metabolism in individuals at metabolic risk for Alzheimer's Disease (AD). The FIGHT-AD trial will provide critical data to inform the design of future clinical trials targeting metabolic and brain health through HT.nnCLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT06023407.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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Heat therapy (HT) has been shown to improve peripheral blood glucose regulation in some populations, yet its effects on brain glucose metabolism remain largely unexplored. The chronic benefits of HT may arise in part from upregulation of heat-shock proteins (HSPs). These proteins play a crucial role in the stress response and modulate diverse processes such as proteostasis and cell signaling pathways, including that of insulin signaling. Understanding the impact of HT on both peripheral and central glucose metabolism, including the effects of varying temperatures, is essential for elucidating potential mechanisms underlying its brain benefits. The Feasibility of Improving Glycemia to prevent Alzheimer's Disease (FIGHT-AD) study is a randomized controlled trial that aims to investigate changes in blood and brain glucose regulation following 10 weeks of HT. Specifically, we will examine the peripheral biomarker responses to warm and hot HT and assess how these responses relate to brain metabolic changes in both treatment groups. This trial will be the first to quantify the effect of HT on cerebral glucose metabolism in individuals at metabolic risk for Alzheimer's Disease (AD). The FIGHT-AD trial will provide critical data to inform the design of future clinical trials targeting metabolic and brain health through HT.nnCLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT06023407.
Honea, Robyn A; Patel, Ankit; Guiler, William; D'Esposito, Mark; Chapman, Sandra Bond; Cook, Lori G; Spence, Jeffrey S
Longitudinal Surface-Based Morphometry Reveals Potential MRI Biomarkers Correlated with Multidimensional Brain Health Measures Journal Article
In: Res Sq, 2025, ISSN: 2693-5015.
@article{pmid41333417,
title = {Longitudinal Surface-Based Morphometry Reveals Potential MRI Biomarkers Correlated with Multidimensional Brain Health Measures},
author = {Robyn A Honea and Ankit Patel and William Guiler and Mark D'Esposito and Sandra Bond Chapman and Lori G Cook and Jeffrey S Spence},
doi = {10.21203/rs.3.rs-8088216/v1},
issn = {2693-5015},
year = {2025},
date = {2025-11-01},
journal = {Res Sq},
abstract = {Characterizing longitudinal brain changes linked to brain health requires identifying structural and neuroanatomical biomarkers. This study aimed to discover MRI-based biomarkers for the Brain Health Index (BHI), a multidimensional measure of cognition, emotional well-being, and social connectedness, and assess their feasibility as indicators of brain health improvement. We investigated neuroanatomical correlates of BHI using longitudinal surface-based morphometry in 210 healthy adults (aged 20-70). We hypothesized that baseline brain morphology would predict BHI performance and that longitudinal BHI changes would correlate with morphometric changes. Participants underwent up to five MRI scans over four years. Surface-based analyses quantified changes in cortical volume, thickness, sulcal depth (SD), gyrification index (GI), and fractal dimension (FD). Vertex-wise regressions tested associations between baseline BHI and morphometric changes, and between longitudinal BHI changes and morphometric features, controlling for age, sex, education, and scan interval. In males, baseline BHI predicted increased FD in the left inferior parietal cortex. In the whole group, BHI gains correlated with increased GI in the left insula and posterior cingulate. In females, BHI improvements were linked to greater SD in the left precuneus, middle temporal, and right cingulate gyri. A sex-specific interaction showed BHI gains in males associated with increased GI in the left insula and temporal cortices. These findings highlight FD, GI, and SD as potential MRI biomarkers for tracking changes in brain health, revealing sex-specific neuroanatomical associations with BHI improvements in regions such as the insula and precuneus.},
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pubstate = {published},
tppubtype = {article}
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Characterizing longitudinal brain changes linked to brain health requires identifying structural and neuroanatomical biomarkers. This study aimed to discover MRI-based biomarkers for the Brain Health Index (BHI), a multidimensional measure of cognition, emotional well-being, and social connectedness, and assess their feasibility as indicators of brain health improvement. We investigated neuroanatomical correlates of BHI using longitudinal surface-based morphometry in 210 healthy adults (aged 20-70). We hypothesized that baseline brain morphology would predict BHI performance and that longitudinal BHI changes would correlate with morphometric changes. Participants underwent up to five MRI scans over four years. Surface-based analyses quantified changes in cortical volume, thickness, sulcal depth (SD), gyrification index (GI), and fractal dimension (FD). Vertex-wise regressions tested associations between baseline BHI and morphometric changes, and between longitudinal BHI changes and morphometric features, controlling for age, sex, education, and scan interval. In males, baseline BHI predicted increased FD in the left inferior parietal cortex. In the whole group, BHI gains correlated with increased GI in the left insula and posterior cingulate. In females, BHI improvements were linked to greater SD in the left precuneus, middle temporal, and right cingulate gyri. A sex-specific interaction showed BHI gains in males associated with increased GI in the left insula and temporal cortices. These findings highlight FD, GI, and SD as potential MRI biomarkers for tracking changes in brain health, revealing sex-specific neuroanatomical associations with BHI improvements in regions such as the insula and precuneus.
Kueck, Paul J; Honea, Robyn A; Kemna, Riley E; Burns, Jeffrey M; Morris, Jill K
Brain-derived neurotrophic factor and its relationship to known biomarkers of Alzheimer's disease Journal Article
In: J Alzheimers Dis, pp. 13872877251362487, 2025, ISSN: 1875-8908.
@article{pmid40734462,
title = {Brain-derived neurotrophic factor and its relationship to known biomarkers of Alzheimer's disease},
author = {Paul J Kueck and Robyn A Honea and Riley E Kemna and Jeffrey M Burns and Jill K Morris},
doi = {10.1177/13872877251362487},
issn = {1875-8908},
year = {2025},
date = {2025-07-01},
journal = {J Alzheimers Dis},
pages = {13872877251362487},
abstract = { Brain-derived neurotrophic factor (BDNF) is involved in neuronal survival and synaptic plasticity, but can be released by platelets, confounding its measurement. We aimed to compare BDNF concentrations following different processing strategies. We analyzed BDNF in 99 older adults with and without cognitive impairment. Processing EDTA plasma normally (PRP) resulted in different values than removing platelets (PPP). Cognitively impaired participants had lower BDNF compared to controls in PPP, while PRP BDNF showed no differences. A positive relationship was evident between PPP BDNF and AD biomarkers measured in PRP. Our findings suggest that circulating BDNF may be a compensatory mechanism in impaired participants and underscore the importance of blood pre-processing strategies.},
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tppubtype = {article}
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Brain-derived neurotrophic factor (BDNF) is involved in neuronal survival and synaptic plasticity, but can be released by platelets, confounding its measurement. We aimed to compare BDNF concentrations following different processing strategies. We analyzed BDNF in 99 older adults with and without cognitive impairment. Processing EDTA plasma normally (PRP) resulted in different values than removing platelets (PPP). Cognitively impaired participants had lower BDNF compared to controls in PPP, while PRP BDNF showed no differences. A positive relationship was evident between PPP BDNF and AD biomarkers measured in PRP. Our findings suggest that circulating BDNF may be a compensatory mechanism in impaired participants and underscore the importance of blood pre-processing strategies.
Kemna, Riley E; Kueck, Paul J; Honea, Robyn; Clark, Zachary; Rekowski, Michaella; Weidling, Ian; Mayfield, Hana; John, Casey S; Burns, Jeffrey; Wilkins, Heather M; Swerdlow, Russell; Morris, Jill K
Mitochondrial DNA affects tau phosphorylation in aging and Alzheimer's disease Journal Article
In: Alzheimers Dement, vol. 21, no. 7, pp. e70390, 2025, ISSN: 1552-5279.
@article{pmid40596736,
title = {Mitochondrial DNA affects tau phosphorylation in aging and Alzheimer's disease},
author = {Riley E Kemna and Paul J Kueck and Robyn Honea and Zachary Clark and Michaella Rekowski and Ian Weidling and Hana Mayfield and Casey S John and Jeffrey Burns and Heather M Wilkins and Russell Swerdlow and Jill K Morris},
doi = {10.1002/alz.70390},
issn = {1552-5279},
year = {2025},
date = {2025-07-01},
journal = {Alzheimers Dement},
volume = {21},
number = {7},
pages = {e70390},
abstract = {INTRODUCTION: Impaired mitochondrial function is seen in Alzheimer's disease (AD), but its role is unclear. Mitochondrial DNA (mtDNA) supports bioenergetic metabolism, but it is uncertain how it might influence AD neuropathology.nnMETHODS: We used cytoplasmic hybrid (cybrid) cell lines made from SH-SY5Y cells expressing mtDNA from cognitively healthy (CH), mild cognitive impairment (MCI), or AD individuals to investigate the impact of mtDNA-determined mitochondrial function on amyloid, tau, and neurodegeneration (ATN) markers. Cybrid measurements were correlated with cognition and brain morphometry.nnRESULTS: Relative to cybrids expressing mtDNA from CH individuals, MCI and AD cybrids contained more phosphorylated tau-217 (p-tau217), p-tau181, and total tau. Cybrid p-tau217 correlated with plasma p-tau217 from the mtDNA donor (β = 0.605, p < 0.001). We observed negative relationships between cybrid p-tau217 and cognition and brain morphometry. MCI and AD cybrid proteomes showed mitochondrial dysfunction.nnDISCUSSION: mtDNA-determined mitochondrial function affects cell physiology in AD-relevant ways. Our study suggests that mtDNA affects ATN status and clinical state.nnHIGHLIGHTS: Mitochondrial DNA (mtDNA)-determined mitochondrial function drives Alzheimer's disease (AD) hallmarks. Cytoplasmic hybrid outcomes associate with mtDNA-donor clinical measures. Proteomic analyses indicate mitochondrial dysfunction in AD.},
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pubstate = {published},
tppubtype = {article}
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INTRODUCTION: Impaired mitochondrial function is seen in Alzheimer's disease (AD), but its role is unclear. Mitochondrial DNA (mtDNA) supports bioenergetic metabolism, but it is uncertain how it might influence AD neuropathology.nnMETHODS: We used cytoplasmic hybrid (cybrid) cell lines made from SH-SY5Y cells expressing mtDNA from cognitively healthy (CH), mild cognitive impairment (MCI), or AD individuals to investigate the impact of mtDNA-determined mitochondrial function on amyloid, tau, and neurodegeneration (ATN) markers. Cybrid measurements were correlated with cognition and brain morphometry.nnRESULTS: Relative to cybrids expressing mtDNA from CH individuals, MCI and AD cybrids contained more phosphorylated tau-217 (p-tau217), p-tau181, and total tau. Cybrid p-tau217 correlated with plasma p-tau217 from the mtDNA donor (β = 0.605, p < 0.001). We observed negative relationships between cybrid p-tau217 and cognition and brain morphometry. MCI and AD cybrid proteomes showed mitochondrial dysfunction.nnDISCUSSION: mtDNA-determined mitochondrial function affects cell physiology in AD-relevant ways. Our study suggests that mtDNA affects ATN status and clinical state.nnHIGHLIGHTS: Mitochondrial DNA (mtDNA)-determined mitochondrial function drives Alzheimer's disease (AD) hallmarks. Cytoplasmic hybrid outcomes associate with mtDNA-donor clinical measures. Proteomic analyses indicate mitochondrial dysfunction in AD.
Mansel, Clayton; Mazzotti, Diego R; Townley, Ryan; Sardiu, Mihaela E; Swerdlow, Russell H; Honea, Robyn A; Veatch, Olivia J
Distinct medical and substance use histories associate with cognitive decline in Alzheimer's disease Journal Article
In: Alzheimers Dement, vol. 21, no. 3, pp. e70017, 2025, ISSN: 1552-5279.
@article{pmid40110639,
title = {Distinct medical and substance use histories associate with cognitive decline in Alzheimer's disease},
author = {Clayton Mansel and Diego R Mazzotti and Ryan Townley and Mihaela E Sardiu and Russell H Swerdlow and Robyn A Honea and Olivia J Veatch},
doi = {10.1002/alz.70017},
issn = {1552-5279},
year = {2025},
date = {2025-03-01},
urldate = {2025-03-01},
journal = {Alzheimers Dement},
volume = {21},
number = {3},
pages = {e70017},
abstract = {INTRODUCTION: Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's disease (AD) diagnosis.nnMETHODS: Self-reported medical and substance use history (i.e., problem history) was used to cluster participants from the National Alzheimer's Coordinating Center (NACC) into distinct subtypes. Linear mixed effects modeling was used to determine the effect of problem history subtype on cognitive decline over 2 years.nnRESULTS: Two thousand seven hundred fifty-four individuals were partitioned into three subtypes: minimal (n = 1380), substance use (n = 1038), and cardiovascular (n = 336). The cardiovascular problem history subtype had significantly worse cognitive decline over a 2 year follow-up period (p = 0.013).nnDISCUSSION: Our study highlights the need to account for problem history to reduce heterogeneity of outcomes in AD clinical trials.nnHIGHLIGHTS: Clinical data were used to identify subtypes of patients with Alzheimer's disease (AD) in the National Alzheimer's Coordinating Center dataset. Three problem history subtypes were found: minimal, substance use, and cardiovascular. The mean change in Clinical Dementia Rating Sum of Boxes (CDR-SB) was assessed over a 2 year follow-up. The cardiovascular subtype was associated with the worst cognitive decline. The magnitude of change in CDR-SB was similar to recent AD clinical trials.},
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INTRODUCTION: Phenotype clustering reduces patient heterogeneity and could be useful when designing precision clinical trials. We hypothesized that the onset of early cognitive decline in patients would exhibit variance predicated on the clinical history documented prior to an Alzheimer's disease (AD) diagnosis.nnMETHODS: Self-reported medical and substance use history (i.e., problem history) was used to cluster participants from the National Alzheimer's Coordinating Center (NACC) into distinct subtypes. Linear mixed effects modeling was used to determine the effect of problem history subtype on cognitive decline over 2 years.nnRESULTS: Two thousand seven hundred fifty-four individuals were partitioned into three subtypes: minimal (n = 1380), substance use (n = 1038), and cardiovascular (n = 336). The cardiovascular problem history subtype had significantly worse cognitive decline over a 2 year follow-up period (p = 0.013).nnDISCUSSION: Our study highlights the need to account for problem history to reduce heterogeneity of outcomes in AD clinical trials.nnHIGHLIGHTS: Clinical data were used to identify subtypes of patients with Alzheimer's disease (AD) in the National Alzheimer's Coordinating Center dataset. Three problem history subtypes were found: minimal, substance use, and cardiovascular. The mean change in Clinical Dementia Rating Sum of Boxes (CDR-SB) was assessed over a 2 year follow-up. The cardiovascular subtype was associated with the worst cognitive decline. The magnitude of change in CDR-SB was similar to recent AD clinical trials.
Kulminski, Alexander M; Jain-Washburn, Ethan; Nazarian, Alireza; Wilkins, Heather M; Veatch, Olivia; Swerdlow, Russell H; Honea, Robyn A
Association of APOE alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer's disease neuroimaging markers Journal Article
In: Alzheimers Dement, vol. 21, no. 2, pp. e14445, 2025, ISSN: 1552-5279.
@article{pmid39713891,
title = {Association of APOE alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer's disease neuroimaging markers},
author = {Alexander M Kulminski and Ethan Jain-Washburn and Alireza Nazarian and Heather M Wilkins and Olivia Veatch and Russell H Swerdlow and Robyn A Honea},
doi = {10.1002/alz.14445},
issn = {1552-5279},
year = {2025},
date = {2025-02-01},
journal = {Alzheimers Dement},
volume = {21},
number = {2},
pages = {e14445},
abstract = {INTRODUCTION: TOMM40 and APOC1 variants can modulate the APOE-ε4-related Alzheimer's disease (AD) risk by up to fourfold. We aim to investigate whether the genetic modulation of ε4-related AD risk is reflected in brain morphology.nnMETHODS: We tested whether 27 magnetic resonance imaging-derived neuroimaging markers of neurodegeneration (volume and thickness in temporo-limbic regions) are associated with APOE-TOMM40-APOC1 polygenic profiles using the National Alzheimer's Coordinating Center Uniform Data Set linked to the AD Genetic Consortium data.nnRESULTS: All brain regions studied using structural phenotypes were smaller in individuals with AD. The ε4 allele was associated with smaller limbic (entorhinal, hippocampus, parahippocampus) brain volume and cortical thickness in AD cases than controls. There were significant differences in the associations for the higher-risk and lower-risk ε4-bearing APOE-TOMM40-APOC1 profiles with temporo-limbic region markers.nnDISCUSSION: The APOE-AD heterogeneity may be partly attributed to the modulating role of the TOMM40 and APOC1 genes in the APOE cluster.nnHIGHLIGHTS: The ε4 allele is associated with smaller values of neuroimaging markers in AD cases. Larger values of neuroimaging markers may protect against AD in the ε4 carriers. TOMM40 and APOC1 variants differentiate AD risk in the ε4 carriers. The same variants can differentiate the links between ε4 and neuroimaging markers.},
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INTRODUCTION: TOMM40 and APOC1 variants can modulate the APOE-ε4-related Alzheimer's disease (AD) risk by up to fourfold. We aim to investigate whether the genetic modulation of ε4-related AD risk is reflected in brain morphology.nnMETHODS: We tested whether 27 magnetic resonance imaging-derived neuroimaging markers of neurodegeneration (volume and thickness in temporo-limbic regions) are associated with APOE-TOMM40-APOC1 polygenic profiles using the National Alzheimer's Coordinating Center Uniform Data Set linked to the AD Genetic Consortium data.nnRESULTS: All brain regions studied using structural phenotypes were smaller in individuals with AD. The ε4 allele was associated with smaller limbic (entorhinal, hippocampus, parahippocampus) brain volume and cortical thickness in AD cases than controls. There were significant differences in the associations for the higher-risk and lower-risk ε4-bearing APOE-TOMM40-APOC1 profiles with temporo-limbic region markers.nnDISCUSSION: The APOE-AD heterogeneity may be partly attributed to the modulating role of the TOMM40 and APOC1 genes in the APOE cluster.nnHIGHLIGHTS: The ε4 allele is associated with smaller values of neuroimaging markers in AD cases. Larger values of neuroimaging markers may protect against AD in the ε4 carriers. TOMM40 and APOC1 variants differentiate AD risk in the ε4 carriers. The same variants can differentiate the links between ε4 and neuroimaging markers.
Honea, Robyn A; Wilkins, Heather; Hunt, Suzanne L; Kueck, Paul J; Burns, Jeffrey M; Swerdlow, Russell H; Morris, Jill K
TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging Journal Article
In: Aging Brain, vol. 7, pp. 100134, 2025, ISSN: 2589-9589.
@article{pmid39760103,
title = {TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging},
author = {Robyn A Honea and Heather Wilkins and Suzanne L Hunt and Paul J Kueck and Jeffrey M Burns and Russell H Swerdlow and Jill K Morris},
doi = {10.1016/j.nbas.2024.100134},
issn = {2589-9589},
year = {2025},
date = {2025-01-01},
journal = {Aging Brain},
volume = {7},
pages = {100134},
abstract = {A growing amount of data has implicated the gene in the risk for Alzheimer's disease (AD), neurodegeneration, and accelerated aging. No studies have investigated the relationship of rs2075650 ('650 on the structural complexity of the brain or plasma markers of neurodegeneration. We used a comprehensive approach to quantify the impact of '650 on brain morphology and multiple cortical attributes in cognitively unimpaired (CU) individuals. We also tested whether the presence of the risk allele, G, of '650 was associated with plasma markers of amyloid, tau, and neurodegeneration and if there were interactions with age and sex, controlling for the effects of ε4. We found that the '650 G-allele was associated with decreased sulcal depth, increased gyrification index, and decreased gray matter volume. NfL, GFAP, and pTau181 had independent and age-associated increases in individuals with a G-allele. Our data suggest that '650 is associated with aging-related plasma biomarkers and brain structure variation in temporal-limbic circuits.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A growing amount of data has implicated the gene in the risk for Alzheimer's disease (AD), neurodegeneration, and accelerated aging. No studies have investigated the relationship of rs2075650 ('650 on the structural complexity of the brain or plasma markers of neurodegeneration. We used a comprehensive approach to quantify the impact of '650 on brain morphology and multiple cortical attributes in cognitively unimpaired (CU) individuals. We also tested whether the presence of the risk allele, G, of '650 was associated with plasma markers of amyloid, tau, and neurodegeneration and if there were interactions with age and sex, controlling for the effects of ε4. We found that the '650 G-allele was associated with decreased sulcal depth, increased gyrification index, and decreased gray matter volume. NfL, GFAP, and pTau181 had independent and age-associated increases in individuals with a G-allele. Our data suggest that '650 is associated with aging-related plasma biomarkers and brain structure variation in temporal-limbic circuits.
scholarly Collaborations and inquiries
Dr. Honea welcomes inquiries from researchers, scholars, writers, podcast hosts, and media professionals whose work intersects with brain aging, Alzheimer’s disease, neuroimaging, genetics, lifestyle, resilience, and the human dimensions of neuroscience.
This may include scholarly collaborations, invited talks, podcast interviews, writing opportunities, media conversations, or future academic projects.
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