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Age- and sex-effects on tau-PET binding in the absence of beta-amyloid pathology

Poster No:

888

Submission Type:

Abstract Submission

Authors:

Diana Hobbs¹, Brian Gordon¹, Shaney Flores¹, Sarah Keefe¹, Nicole McKay¹, Julie Wisch¹, Russ Hornbeck¹, Erin Franklin¹, Chengjie Xiong¹, John Morris¹, Richard Perrin¹, Beau Ances¹, Yi Su², Hillary Protas², Tammie Benzinger¹

Institutions:

¹Washington University in St. Louis School of Medicine, St. Louis, MO, ²Banner Health, Phoenix, AZ

First Author:

Diana Hobbs
Washington University in St. Louis School of Medicine
St. Louis, MO

Co-Author(s):

Brian Gordon
Washington University in St. Louis School of Medicine
St. Louis, MO

Shaney Flores, M.S.
Washington University in St. Louis School of Medicine
St. Louis, MO

Sarah Keefe, B.A.
Washington University in St. Louis School of Medicine
St. Louis, MO

Nicole McKay, PhD
Washington University in St. Louis School of Medicine
St. Louis, MO

Julie Wisch
Washington University in St. Louis School of Medicine
St. Louis, MO

Russ Hornbeck, M.S., M.B.A.
Washington University in St. Louis School of Medicine
St. Louis, MO

Erin Franklin
Washington University in St. Louis School of Medicine
St. Louis, MO

Chengjie Xiong, PhD
Washington University in St. Louis School of Medicine
St. Louis, MO

John Morris, MD
Washington University in St. Louis School of Medicine
St. Louis, MO

Richard Perrin, PhD
Washington University in St. Louis School of Medicine
St. Louis, MO

Beau Ances, MD, PhD
Washington University in St. Louis School of Medicine
St. Louis, MO

Yi Su
Banner Health
Phoenix, AZ

Hillary Protas
Banner Health
Phoenix, AZ

Tammie Benzinger
Washington University in St. Louis School of Medicine
St. Louis, MO

Introduction:

Tau PET imaging is a critical tool in Alzheimer disease (AD) research, offering insights into tau deposition across the brain. In addition to understanding Alzheimer disease severity, tau PET can offer insight into the prevalence of tau pathology across the lifespan in individuals who are not on the AD trajectory. Here, we characterize primary age-related tauopathy (PART) in individuals without elevated amyloid levels, and explore whether levels of this protein differ by sex.

Methods:

This study analyzed 251 cognitively unimpaired participants 45-91 years of age from the Knight Alzheimer Disease Research Center (Knight ADRC). Each participant underwent amyloid PET imaging to confirm their amyloid burden was below pathological levels as determined by GMM (SUVR <= 17.15). Tau burden was quantified using PET imaging (18F-flortaucipir), and statistical models were deployed to evaluate the influence of age, sex, race, and subthreshold amyloid burden on regional tau distribution. To strengthen the validity of our findings, we replicated the analyses in an independent cohort of 458 cognitively unimpaired individuals (aged 50-94) from the Alzheimer Disease Neuroimaging Initiative (ADNI).

Results:

Significant positive associations between tau PET binding and age occurred in 7 (Knight ADRC₁) and 13 (ADNI₂) regions, with the largest effects seen in the putamen (t₁=9.40; t₂=10.50) and pallidum (t₁=8.36; t₂=7.39). Elevated tracer uptake in females was present in 19 (Knight ADRC₁) and 12 (ADNI₂) regions, but most prominently in the lateral occipital (t₁=6.67; t₂=4.31), pars orbitalis (t₁=4.93; t₂=4.75), rostral middle frontal (t₁=4.73; t₂=4.85), and the frontal pole (t₁=4.59; t₂=5.31). No statistically significant influence of race or subthreshold amyloid burden was observed for either cohort.

Supporting Image: Screenshot2024-12-18at102034AM.png

Conclusions:

Overall, we confirmed that tau PET is sensitive to age-related tau accumulation and revealed a distribution pattern consistent with the neuropathological features of PART. Additionally, we observed a pronounced sex difference such that women had consistently higher tracer uptake across multiple brain regions. This elevated binding in females suggests that previously reported increases in tau-burden for females is not merely an implication of AD pathology, but rather reflects a widespread, intrinsic phenomenon. However, notable age-associated increases were also observed in the basal ganglia, areas known for off-target binding. Together, these results underscore the importance of disentangling the effects of sex and age on tau PET binding to better assess the utility of these tracers, and also suggest that analyses must carefully consider regional patterns of off-target binding when interpreting 18F-flortaucipir-derived tau PET images. A deeper understanding of these influences is essential for accurately interpreting tau imaging data, particularly in distinguishing normal aging from disease related changes.

Lifespan Development:

Aging ¹

Modeling and Analysis Methods:

PET Modeling and Analysis ²

Keywords:

ADULTS

Aging

Data analysis

Degenerative Disease

DISORDERS

Neurological

Positron Emission Tomography (PET)

Structures

^1|2Indicates the priority used for review

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