# Post-doctoral fellowship in the mechanisms of age-related tauopathy

> **NIH NIH F32** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $67,292

## Abstract

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease associated with the presence of
both amyloid beta peptide (Aβ) containing-plaques and neurofibrillary tangles (NFT) in the cortical region of
brain tissue. In 2015, a new consensus criteria established by our group, in collaboration with a large group of
prominent neuropathologists and neuroscientists, defined a new category of Alzheimer's disease (AD)
neuropathologic changes termed primary age-related tauopathy (PART). Post-mortem neuropathological
examination of individuals with PART reveals tissues lacking amyloid beta peptide (Aβ) containing-plaques, but
still containing a number of AD-type NFTs. Patients with PART may have normal cognition, amnestic mild
cognitive impairment (aMCI), or an amnestic dementia. The prevalence of PART dementia is unclear, with
estimates ranging from 1-7%, but PART is likely more pervasive. Studies investigating the genetics and
biochemical mechanisms of PART will have a profound impact in understanding the regional vulnerability of
the temporal lobe and the broad pathogenesis of tauopathies. We hypothesize that subjects with PART have
distinct characteristics that underlie their NFT+/Aβ- phenotype. In our first aim we will validate
neuropathological criteria for PART and lay the groundwork for clinical and mechanistic studies that will
elucidate disease burden, pathogenesis and progression. Brain tissue collected from dozens of domestic and
international brain banks will be stained, imaged, and quantification of NFT burden will be performed using
quantitative and semi-quantitative techniques as well as stereology. In the second aim we will test the
hypothesis that PART has a genetic risk profile that overlaps with some aspects of AD genetics (e.g., MAPT
haplotypes) but diverges with respect to others (e.g., APOE genotype). To accomplish this aim we will execute
a genome wide association (GWA) study comparing frequency of known AD risk alleles in PART, AD and
controls using DNA isolated from the tissue collected in aim one. Lastly, we will study and compare the onset
and progression of PART using genetically manipulated iPSC cultures. This will explore the role PART-related
genetics play in tauopathic disorders, and create a model cell line from iPSCs which will be used to further
study how these genetic changes influence cell phenotype and genotype. In summary, the clinical-translational
research performed in this study will establish PART as an Aβ-independent process with a unique
neuropathological, biochemical, and genetic signature that distinguishes it from AD and other tauopathies.

## Key facts

- **NIH application ID:** 9830531
- **Project number:** 5F32AG056098-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Kurt William Farrell
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,292
- **Award type:** 5
- **Project period:** 2017-12-01 → 2020-11-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830531

## Citation

> US National Institutes of Health, RePORTER application 9830531, Post-doctoral fellowship in the mechanisms of age-related tauopathy (5F32AG056098-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9830531. Licensed CC0.

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