# Depression and Alzheimer's Disease:  CaTAUstrophy?

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $821,468

## Abstract

ABSTRACT
Better understanding the interface of depression and Alzheimer’s Disease (AD) pathology could
lead to new strategies to prevent or slow cognitive decline, with significant public health impact.
Depression has historically been neglected and/or excluded in observational cohort and clinical
trial research on AD– so we have limited knowledge about its relationship with pathological
hallmarks of AD and cognitive decline. Our data suggest an association between tau and
depression that may potentiate cognitive decline in preclinical stages of AD—when amyloid are
below PET positivity thresholds--and confer dementia risk. Currently, the model of tau-
associated depressive symptoms needs to be validated across the full spectrum of depressive
symptom severity, including major depressive disorder (MDD). The current study was designed
to address this critical gap. Our overarching goal is to investigate the relationships between tau
and depressive symptoms over time in cognitively unimpaired older adults using both
longitudinal tau PET (with spatiotemporal resolution) and novel plasma tau measures (with
greater potential for clinical translation than PET or CSF) that are gaining rapid readiness for
clinical translation). Achieving this goal will help characterize risk of cognitive decline for older
adults with clinically significant depressive symptoms, optimize approaches to depression
evaluation, and provide potential opportunities for early recognition and prevention of AD. Our
primary hypothesis is that tau in temporal brain regions will predict more severe depressive
symptoms, and that greater depressive symptoms will potentiate tau-associated cognitive
decline. We will test these hypotheses in 150 cognitively unimpaired older adults across the
spectrum of depression (subclinical to Major Depressive Disorder [MDD]) integrating
longitudinal affective and cognitive symptom characterization, tau PET, and tau plasma
biomarker assessments.This is the first study to our knowledge to investigate longitudinal tau
PET and plasma measures in a cohort of older adults across the full range of depressive
symptom severity. Better understanding of the mechanisms underlying depressive symptoms in
preclinical AD could inform prevention efforts, including tau measurement as a means of
identifying risk in older adults with late life depression. Thus, we will address the FOA goal “to
encourage biomedical, behavioral and social sciences research that will enhance knowledge of
mechanisms underlying neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) or
Alzheimer's disease-related dementias (ADRD) so as to enable novel treatment development.”

## Key facts

- **NIH application ID:** 10499778
- **Project number:** 1R01AG078191-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jennifer Rose Gatchel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $821,468
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499778

## Citation

> US National Institutes of Health, RePORTER application 10499778, Depression and Alzheimer's Disease:  CaTAUstrophy? (1R01AG078191-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499778. Licensed CC0.

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