# Resilience to Alzheimer's disease in humans with exceptional longevity

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $1,244,549

## Abstract

Project Summary/Abstract:
Prior research efforts that focused on identifying the risks for Alzheimer's disease (AD) have not
resulted in effective treatments. This led to a growing appreciation of resilience factors that allow
individuals to remain disease-free despite having risk factors for AD. Centenarians are a
population enriched with AD resilience, as many maintain normal cognition throughout their
lifespan despite achieving advanced chronological age, a major risk factor for AD, or being
carriers of high-risk AD associated genotypes. For over a decade our research group has
focused on resilience factors that protect centenarians against AD and other age-related
diseases by studying the genetically homogenous population of Ashkenazi Jews and has
identified resilient genotypes that have been implicated in preservation of cognitive function.
Building on our past success of multidisciplinary research and expanding our methodologies to
include integrative network approaches we will test the hypothesis that individuals with
exceptional longevity possess unique genotypes that result in resilience to dementia in
two established longevity studies: (1) Longevity Genes Project (LGP), a cross sectional cohort
of centenarians, who at age 95 had preserved cognitive function, and controls; (2) LonGenity,
an independent, longitudinal study of offspring of centenarians, who are enriched with longevity
genomes, and age-matched controls without parental history of longevity (planned n=1400,
mean age 75) that are followed prospectively with neurocognitive assessments for the incidence
of cognitive decline and AD. This proposal aims to integrate high-level data from these two
longevity cohorts that includes genotypes, whole exome sequencing, biochemical, clinical and
neurocognitive profiles and to interrogate it in an effort to identify cognitive resilience genes
using: (1) gene-gene interaction analysis and (2) network-based integrative analysis. The top
candidates discovered with these integrative approaches will be validated for their association
with resilience in two human cohorts and in neuronal cell models that will be engineered to
harbor the AD-resilience genotypes. By utilizing integrative computational approaches to
analyze high-dimensional data, cell models, as well as validation cohorts, we aim to identify and
validate genotypes and molecular networks that mediate cognitive resilience. Identification of
these factors in resilient human populations has the potential to expedite the development of
effective therapies for AD.

## Key facts

- **NIH application ID:** 9949598
- **Project number:** 5R01AG057909-05
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** NIR J BARZILAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,244,549
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9949598

## Citation

> US National Institutes of Health, RePORTER application 9949598, Resilience to Alzheimer's disease in humans with exceptional longevity (5R01AG057909-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9949598. Licensed CC0.

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