# CA1 cell-type susceptibility in Alzheimer's

> **NIH NIH R36** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $51,652

## Abstract

Abstract
Advanced neuroimaging techniques have shown the impacts of Alzheimer’s disease (AD) pathology
propagation and their structural repercussions in the brain. Recent studies show that unimpaired individuals
who have advanced amyloid and tau pathology in the medial temporal lobe (MTL) are more at risk for
developing mild cognitive impairment (MCI). These discoveries suggest the presence of vulnerable brain
regions that serve as an initial focal point for the spread of AD pathology. Recent developments in
connectomics and spatial transcriptomics now allow us to identify individual cell types within the MTL and
investigate the subcellular molecular changes that occur throughout AD progression. Identifying susceptible
cell types within MTL will reveal potential targets for early treatment intervention. Within the MTL, entorhinal
cortex (ENT) connections with CA1 in the hippocampus are particularly affected by AD and related to cognitive
impairment. From CA1, it is believed that amyloid and tau propagate through neural circuits to other brain
structures, leading to a neurodegenerative cascade as it extends to additional brain regions. Establishing and
characterizing distinct neuronal changes in CA1 projection neuron cell types, in the presence of amyloid, can
reveal novel targets with the aim of mitigating or even halting the progression of AD at its earliest stages. We
hypothesize that a neural circuit from entorhinal CA1 neurons that project to other memory-related brain
structures are specifically susceptibility points to AD. To unveil vulnerable CA1 neurons and understand
alterations in their morphological characteristics, we will used advanced viral tracing methods and cutting-edge
microscopy imaging to identify and reconstruct 3D ENT→CA1 cell-type specific circuits to analyze distinct
pathway changes in AD mouse models. After identifying susceptible cell types, we will use MERFISH spatial
transcriptomics to investigate the molecular changes to AD-relevant genes within CA1 neurons. Overall, this
study will establish cell type specific neural circuits that are susceptible to AD pathology and reveal the
subcellular response of these cell types throughout the progression of disease.

## Key facts

- **NIH application ID:** 10891017
- **Project number:** 1R36AG087310-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Maricarmen Pachicano
- **Activity code:** R36 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $51,652
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891017

## Citation

> US National Institutes of Health, RePORTER application 10891017, CA1 cell-type susceptibility in Alzheimer's (1R36AG087310-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10891017. Licensed CC0.

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