# Molecular Determinants of Age-Related Cognitive Decline in the Basal Forebrain to Lateral Entorhinal Cortex Circuit

> **NIH AG K22** · UNIVERSITY OF GEORGIA · 2026 · $198,352

## Abstract

PROJECT SUMMARY
The entorhinal cortex (EC) is a critical mediator of cortico-hippocampal communication and thus essential for
memory. Numerous studies identify the EC as the first brain region to display age-related changes such as
accumulation of tau protein as related to Alzheimer’s disease (AD). Structural and functional changes to the EC
have been found to precede and even predict future cognitive impairment. The EC is comprised of two
subdivisions that are anatomically and functionally distinct, the lateral EC (LEC) and medial EC (MEC). Human
studies have found that of these, the LEC is the earliest affected by age. I have previously found that loss of
basal forebrain cholinergic input (BFCN) to the LEC is a critical component of LEC-related cognitive impairment
and an early feature of the aging pathology. Cholinergic neurons are essential for normal attention, mood, and
memory. Marked reductions of cholinergic neurons are a hallmark of AD. Despite the importance of each of
these regions to pathological aging, the molecular determinants of the selective and early vulnerability in the
BFCN to EC circuit is not known. The proposed studies will identify molecular signatures of vulnerability and the
sequence of events that ultimately renders the BFCN to EC circuit particularly vulnerable to age. Using
transcriptomics, high-resolution microscopy, and behavioral assays, I will identify the unique signatures of BFCN
and LEC vulnerability in aging. Aim 1 studies will focus on the BFCN, classifying young and aged BFCNs based
on their unique gene expression profiles, identifying LEC-projecting BFCNs, and evaluating the consequences
of targeted LEC disruption on subsequent behavior, BFCN integrity and the BFCN transcriptome. In parallel,
Aim 2 studies will focus on the LEC, classifying young and aged LEC neurons based on their gene expression
profiles, evaluating the integrity of LEC neurons in aged animals, and evaluating the consequences of targeted
BFCN disruption on s

## Key facts

- **NIH application ID:** 10946930
- **Project number:** 1K22AG088111-01
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Mala Rajam Ananth
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** AG
- **Fiscal year:** 2026
- **Award amount:** $198,352
- **Award type:** 1
- **Project period:** 2026-03-15T00:00:00 → 2029-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10946930

## Citation

> US National Institutes of Health, RePORTER application 10946930, Molecular Determinants of Age-Related Cognitive Decline in the Basal Forebrain to Lateral Entorhinal Cortex Circuit (1K22AG088111-01). Retrieved via AI Analytics 2026-07-05 from https://api.ai-analytics.org/grant/nih/10946930. Licensed CC0.

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