# Dissociating the mechanisms of Tau PET and cortical atrophy underlying memory deficits in typical and atypical prodromal Alzheimer's disease

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $180,185

## Abstract

The proposed research examines the mechanisms underlying memory encoding versus storage deficits, in
typical and atypical AD at the stage of mild cognitive impairment, by delineating the specific roles of amyloid,
tau, and cortical atrophy as potential drivers of this impairment both cross-sectionally and longitudinally. A
long-term goal of the research program is to improve clinical prognostication and outcomes monitoring by
expanding our knowledge of the mechanisms of memory encoding impairment across the AD spectrum, with a
focus on better characterizing the atypical presentations of AD (i.e., posterior cortical atrophy; PCA, and
logopenic variant primary progressive aphasia; lvPPA). The proposal builds upon preliminary evidence
showing that memory encoding, in contrast to memory storage, relies on cortical networks outside the medial
temporal lobes in typical and atypical AD, and that auditory-verbal working memory deficits impact encoding
and retrieval, but not storage, in PCA. The candidate’s preliminary work also demonstrated that visual space
and face perception deficits, which may be critical contributors to memory encoding, are sensitive to AD-
related tau and atrophy in visual association regions in PCA and lvPPA. We will build on this preliminary work
by examining these processes in relation to different stages of memory (encoding vs storage), and in relation
to imaging biomarkers of AD pathology. The first aim is to examine the impact of visual or auditory-verbal
processing impairment on associative memory encoding and storage, in relation to tau and amyloid pathology,
across the spectrum of prodromal AD. The second aim is to investigate the mediating effect of cortical atrophy
and moderating factors, including age at symptom onset, that may explain this relationship between tau
pathology and memory. Short-term training goals for these aims include obtaining expertise in tau and amyloid
PET processing that will further the candidate's long-term goal of utilizing multimodal neuroimaging with
cognitive outcome measures to prognosticate disease course across the AD phenotypic spectrum. The third
aim is to determine the longitudinal impact of tau spread on atrophy and progressive memory decline across
the spectrum of prodromal AD. Training for this aim will extend the candidate's expertise into longitudinal
biostatistical analysis, including morphometric analyses to quantify and control for the effect of gray matter loss
in the prodromal AD population. All aims will utilize data collected from the novel associative memory tasks
outlined in the proposed project. All other clinical and neuroimaging data will be provided by the primary
mentor’s NIH-funded studies. Training available at Massachusetts General Hospital and the Harvard Medical
School community allows access to resources and mentorship in the specific techniques necessary to the
completion of the proposed aims and the candidate's training and career goals.

## Key facts

- **NIH application ID:** 10137867
- **Project number:** 5K23AG065450-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Deepti Putcha
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $180,185
- **Award type:** 5
- **Project period:** 2020-04-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137867

## Citation

> US National Institutes of Health, RePORTER application 10137867, Dissociating the mechanisms of Tau PET and cortical atrophy underlying memory deficits in typical and atypical prodromal Alzheimer's disease (5K23AG065450-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10137867. Licensed CC0.

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