# Proj 1 - Interplay between peripheral autophagy and AD in aging

> **NIH NIH P01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $364,531

## Abstract

Summary
 Loss of proteostasis is considered one of the process that contributes to aging. Among the different
components of the proteostasis network, this program project (PP) focuses on Autophagy. During previous
periods we have identified new types of selective autophagy, their interplay among them and with other
components of the proteostasis network, new functions of autophagy beyond proteostasis maintenance,
mechanisms responsible for autophagic pathways’ malfunctioning in aging and the impact of this
malfunctioning in organ proteostasis and function. The knowledge, technology and experimental tools
developed by this PP allow now this project to answer two to fundamental questions in the context of
Geroscience: 1) is there a bi-directional interplay between autophagy in peripheral organs and central nervous
system and does this interconnection explains the non-phsicological comorbilities that associate with
Alzhiemer’s disease and Related Dementias (AD/ADRD)? and 2) can prevention of aging of the autophagic
system attenuate proteotoxicity associated with AD/ADRD, one of the most prevalent diseases of aging?.
 With this purpose and in close collaboration with the other components of this PP we will: 1) determine
if models of AD-related brain proteotoxicity have disturbances in peripheral proteostasis and if that is true in
peripheral patient cells; 2) analyze the effect of aging of the autophagy system in peripheral organs on the
aged brain and in onset of AD-related proteotoxicity 3) investigate the effect of chemical or genetic
enhancement of central and/or peripheral autophagy on brain aging and AD-proteotoxicity.
Integration in the PP: this project will utilize experimental mouse models with AD-relate proteins to
recapitulate the proteotoxicity of the AD brain, and the aging mouse groups generated by the Animal Core and
shared by all the projects. Image-based analysis of the changes in peripheral and central autophagy will be
done with the state-of-the-art image technology provided by the Image Core and treatment of the animal
models with autophagy enhancers will be done with the Therapeutics Core. Mechanisms of
intercommunication between peripheral and central autophagy will be investigated with P2, and the cross-talk
between autophagic pathways with P4. Information on peripheral and central autophagy generated in these
collaborative and on autophagic pathways in in the immune and hematopoietic system generated by P3 in the
same models will be integrated at the Biostatistics Unit.
Relevance to public health: Studies in this project may provide novel information on the bases of other
comorbidities that affect AD/ADRD patients and on how they may contribute also to disease progression. If
successful, the interventions proposed in this work may offer a proof-of-concept and prototype molecules for
future development of drugs for treatment of neurodegenerative conditions that originate from proteotoxic
insults by preventing aging of the autop...

## Key facts

- **NIH application ID:** 10799679
- **Project number:** 5P01AG031782-17
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** ANA MARIA CUERVO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $364,531
- **Award type:** 5
- **Project period:** 2009-02-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799679

## Citation

> US National Institutes of Health, RePORTER application 10799679, Proj 1 - Interplay between peripheral autophagy and AD in aging (5P01AG031782-17). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10799679. Licensed CC0.

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