# Astrocyte Reaction in Alzheimer's Disease

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $167,400

## Abstract

PROJECT SUMMARY/ABSTRACT
 The proposed research focuses on investigating the role of astrocyte reaction in Alzheimer's disease (AD).
Much of AD research has focused on the two pathological hallmarks of the disease -amyloid plaques and
neurofibrillary tangles- and their effects on neurons and synapses. Reactive astrocytes are universally present
in neurodegenerative diseases, and in AD they react to plaques and tangles, but whether they contribute to
neurodegeneration or are neuroprotective remains uncertain.
 The applicant's research strategy aims at a deep phenotyping of astrocytes in AD mouse models and the
human AD brain. The hypothesis to be tested is that astrocyte phenotype changes along the course of AD, from
neuroprotective to neurotoxic, and perhaps senescent astrocytes in the end-stage. Importantly, this project
builds upon prior observations made by the applicant using stereology-based quantitative methods in human
brain specimens, while moving towards experimental grounds and extending his skillset including astrocyte
purification methods, RNA-seq, bioinformatics, astrocyte-specific manipulations in AD mouse models with
viral-mediated gene delivery, novel histological methods (i.e. cyclic immunofluorescence, array tomography),
and biochemical methods (i.e. sequential protein extraction, synaptoneurosome preparations).
 The candidate's research environment is ideal for the project. The Massachusetts General Hospital and
the Harvard Medical School are a nurturing atmosphere for trainees, and have multiple core facilities. The
MassGeneral Institute for Neurodegenerative Diseases and the Massachusetts Alzheimer's Disease Research
Center are first rank infrastructures devoted to research on AD and other neurodegenerative diseases.
 The candidate's mentoring team is composed of a world-class AD researcher (Dr. Bradley Hyman), a
renowned neuropathologist (Dr. Matthew Frosch), and an early PhD investigator with expertise in AD mouse
models and molecular biology tools including viral-mediated gene transfer (Dr. Eloise Hudry). The advisory
team will contribute with expertise in viral-mediated gene transfer (Dr. Xandra Breakefield), astrocyte biology
and pathology (Dr. James Goldman), and RNA-seq and astrocyte synaptic functions (Dr. Beth Stevens).
 The candidate's training plan includes both career development lectures on relevant topics (i.e. grant
writing, scientific communication, and training in responsible conduct of research), as well as a series of
intensive Harvard Catalyst courses that are pertinent to the proposed research (i.e. Certificate in Applied
Biostatistics, Introduction to Omics Research, Introduction to RNA-seq).
 The combination of a nurturing research environment, experienced mentoring and advisory teams, and a
comprehensive training plan, with allow the applicant to fulfill his short and long-range career goals, which
are deciphering the role of astrocyte reaction in AD and transitioning towards an independent clinician
s...

## Key facts

- **NIH application ID:** 10158382
- **Project number:** 5K08AG064039-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Alberto Serrano-Pozo
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $167,400
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158382

## Citation

> US National Institutes of Health, RePORTER application 10158382, Astrocyte Reaction in Alzheimer's Disease (5K08AG064039-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10158382. Licensed CC0.

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