# Protective factors and mechanisms

> **NIH NIH U19** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $1,240,439

## Abstract

RADCO Project 2 Summary
Much of cognitive impairment and dementia research has concentrated on disease mechanisms
and targets for disrupting these. A compelling alternative approach is to delineate naturally
occurring mechanisms of protection. Some centenarians remain cognitively intact despite an
extreme exposure to the strongest risk factor for cognitive impairment and AD, aging. We
hypothesize that these centenarians and some portion of their offspring have protective factors
that lead to such resilience or in some cases, even resistance against cognitive decline and
dementia. With the support of the Administrative, Phenotyping and Biosamples, and
Neuroimaging Cores, and Project 1 (Resilience and Resistance Phenotypes), this 2nd project of
the “Resistance/Resilience to AD in Centenarians and Offspring" (RADCO) study strives to
discover factors and mechanisms protective against cognitive impairment, AD and other
dementias. This project entails three related approaches: genetics (Aim 1), transcriptomic
analyses (Aim 2), and 3D human neural-glial culture models of age-related brain pathology (Aim
3). Our goals are to 1) identify genetic variants and biological mechanisms of resilience/resistance
in centenarian cognitive superagers, 2) predict mechanisms of cognitive resilience and validate
candidate drugs that can enhance the resilience/resistance in human brain cells, and 3) establish
induced pluripotent stem cells (iPSCs) and iPSC-derived 3D brain cell models of the centenarian
superagers to test those mechanisms as well as discover and test others that could be exploitable
for protective therapeutics.

## Key facts

- **NIH application ID:** 10276392
- **Project number:** 1U19AG073172-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Doo Yeon Kim
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,240,439
- **Award type:** 1
- **Project period:** 2021-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276392

## Citation

> US National Institutes of Health, RePORTER application 10276392, Protective factors and mechanisms (1U19AG073172-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10276392. Licensed CC0.

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