# Depression treatment and Aβ dynamics: A study of Alzheimer’s disease risk

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $761,833

## Abstract

PROJECT SUMMARY
 Ten percent of adults over 65 suffer from Alzheimer’s disease (AD), and this number is projected to double by
2050. Thus, understanding and reducing AD risk factors is of critical importance, particularly in the absence of
an effective treatment. Epidemiological evidence suggests that depression throughout the lifespan contributes to
AD risk, although depression in late life also may be part of the dementia prodrome. Clinicopathological studies
have provided robust support for the importance of amyloid-beta (Aβ) deposition in the pathogenesis of AD, and
evidence supports an association between Aβ and depression. However, most studies that have examined the
relationship between MDD and Aβ have included individuals with mild cognitive impairment (MCI),
complicating our understanding of the relationship between MDD and Aβ. Levels of soluble Aβ are influenced
by the presence of deposited Aβ and our preliminary data suggests that they also are associated with the severity
of depression symptoms. Using a number of depression rating scales, our data also show that changes in residual
symptoms in people with geriatric depression who do not have significant cognitive decline are correlated with
Aβ changes in both cerebrospinal fluid (CSF) and plasma. However, the direction and nature of the causal
relationship between MDD symptoms and Aβ peptide levels are unknown. Given the relationship between Aβ
and AD risk, elucidating the relationship between amyloid dynamics and depression symptoms would allow us
to better understand the mechanism for heightened AD risk imparted by MDD. Since the direction of causation
between depression and Aβ is unknown, the only way to understand cause and associated risk is to treat the
depressive symptoms and examine the effects on AD biomarkers in relation to antidepressant treatment
response. We propose to study 90 cognitively-normal older adults with current episode of MDD and no evidence
of MCI in an 8-week, parallel-group, double-blind, placebo-controlled randomized study using the SSRI
antidepressant escitalopram. The hypothesis is that a reduction in depressive symptoms and treatment response
will be associated with an increase in the levels of CSF Aβ40 and Aβ42, as well as a reduction in vascular
dysfunction markers, including platelet activation. The results of the proposed clinical trial will build on our
understanding of the relationship between MDD symptoms and the biological variables implicated in AD, and
thus provide a significant target for reducing AD risk. If successful, this approach might lead to more effective
strategies for reducing the risk of developing AD through more effective treatment of late-life MDD.

## Key facts

- **NIH application ID:** 10889158
- **Project number:** 5R01AG070821-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Nunzio Pomara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $761,833
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889158

## Citation

> US National Institutes of Health, RePORTER application 10889158, Depression treatment and Aβ dynamics: A study of Alzheimer’s disease risk (5R01AG070821-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10889158. Licensed CC0.

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