# Characterization of transcriptome changes in diet-induced progression to METS/T2D to identify earliest and sex-specific neurodegenerative foci for AD development

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2020 · $186,969

## Abstract

Project Summary
 Metabolic resistance (METS) and type II diabetes (T2D) hold one of the strongest associations with AD
development, however, we know little in terms of how, at a precise mechanistic level, this prodromal metabolic
phenotype actually leads to neurodegenerative changes that ultimately result in AD. We know equally little about
how sex contributes in accelerating or slowing this progression and how known sex-specific differences for
METS/T2D and AD affect this relationship. Given that the incidences of both diseases are skyrocketing,
understanding these aspects is critical to develop optimal early/preventative therapeutic interventions for
individuals with METS/T2D, at high risk for AD. However, addressing these questions using single targeted
hypothesis-based approaches is difficult given the multifactorial nature of potential interactions (multiple disease
factors, time, and sex) and is further confounded by changing/incomplete experimental designs across animal
studies. To address these challenges, we seek to study the relationship between METS/T2D progression and
AD in a more global genome-wide manner, coupled with powerful statistics and biochemical measurements to
gain a clearer picture of the METS/T2D-AD relationship. Specifically, we propose to determine alterations in
transcriptome, AD and METS-related mitochondrial, metabolic, and pathology changes, in both sexes, over time.
We will use bioinformatics and large-scale statistical analysis tools to identify associations across these
variables, in addition to sex hormone levels, and time. We will couple these observations with modifications of
mitochondrial and metabolic genes (affected early in both diseases) and novel ones discovered via RNA seq to
interrogate these relationships mechanistically in vitro.

## Key facts

- **NIH application ID:** 10359377
- **Project number:** 7R21AG064479-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Gemma Casadesus
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $186,969
- **Award type:** 7
- **Project period:** 2019-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359377

## Citation

> US National Institutes of Health, RePORTER application 10359377, Characterization of transcriptome changes in diet-induced progression to METS/T2D to identify earliest and sex-specific neurodegenerative foci for AD development (7R21AG064479-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10359377. Licensed CC0.

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