# Depressive symptoms in the pathogenesis of preclinical Alzheimer's Disease

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $193,453

## Abstract

PROJECT SUMMARY/ABSTRACT:
The candidate is a geriatric psychiatrist with previous basic science training in molecular neurodegeneration
who is applying for a K23 Mentored Patient-Oriented Career Development Award to transition to full
independence as a clinical research scientist. The training goals—gaining expertise in positron emission
tomography (PET) neuroimaging-clinical correlations, clinical research methodology and analytic methods, and
cognitive and behavioral assessments in older adults—will together enable the candidate to emerge as a fully
independent clinician scientist in geriatric psychiatry at the interface of late life depression and preclinical
Alzheimer’s Disease (AD).These training goals are aligned with the aims of the proposed project, which
focuses on late life depressive symptoms in the pathogenesis of preclinical AD. Despite the prevalence of late
life depressive symptoms and AD, the associations among depressive symptoms, in vivo amyloid and tau, and
early clinical manifestations of AD (e.g., subjective cognitive decline, subtle decline on sensitive cognitive tests)
have not been clearly established. This project will fill a critical gap in knowledge by determining whether the
presence (vs absence) of depressive symptoms predicts greater accumulation of AD proteinopathies, amyloid
and tau, and more rapid clinical progression. Preliminary data generated through competitive pilot funding to
the applicant showed a modest cross-sectional association between increased subclinical depressive
symptoms and increased inferior temporal tau (measured using a promising tau PET ligand Flortaucipir [FTP])
in cognitively normal (CN) older adults in the Harvard Aging Study (HABS), one of the best characterized
longitudinal cohorts of preclinical AD. However, further investigation across a wider range of depressive
symptoms and with longitudinal follow up is needed to more definitively address this question. The overarching
hypothesis of the current study is that depressive symptoms, whether cause or consequence of AD pathology,
occur late in preclinical AD and are a marker for greater tau accumulation and clinical progression over time.
To test this hypothesis, we will investigate the cross-sectional association of depressive symptoms and in vivo
cortical amyloid using Pittsburgh compound B (PiB) PET imaging and tau using FTP PET. We will additionally
investigate whether baseline severity of depressive symptoms and cortical amyloid predict greater tau
accumulation over three-year follow up. Finally, we will recruit a new pilot cohort of participants of comparable
cognitive status to HABS but with moderate to severe depressive symptoms in order to investigate whether
depressive symptom severity modifies the relationship between tau and clinical manifestations of AD over
three-year follow up. Together, these aims have promise to impact the design and future success of
prevention trials in older adults who may be at greatest risk for AD, a...

## Key facts

- **NIH application ID:** 9895605
- **Project number:** 5K23AG058805-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jennifer Rose Gatchel
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,453
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895605

## Citation

> US National Institutes of Health, RePORTER application 9895605, Depressive symptoms in the pathogenesis of preclinical Alzheimer's Disease (5K23AG058805-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895605. Licensed CC0.

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