# Cell-specific changes of laminin expression in the CNS in Alzheimer’s disease

> **NIH NIH R21** · UNIVERSITY OF SOUTH FLORIDA · 2021 · $411,125

## Abstract

Project Summary/Abstract
The long-term objectives of this application are to: (1) determine how each individual cell type-derived
laminin changes in the basement membrane (BM) under both physiological and pathological conditions,
and (2) correlate these laminin alterations with AD pathology to screen for unique laminin changes that
are useful in early AD diagnosis (before the onset of dementia or Aβ/tau pathology) and prognosis
prediction. This proposal aims to generate an innovative laminin knock-in mouse line that enables
accurate assessment of laminin expression in a cell-specific and Cre-dependent manner; and
determine the temporary and spatial expression profile of each individual cell type-derived laminin in
the BM in normal and AD brains. We have successfully generated the Laminin-mCherry/eGFP knock-in
mouse line using CRISPR-Cas9 technique and further validated these mice in the presence and
absence of Cre recombination. In Aim 1, we will cross these laminin knock-in mice with various Cre
lines to generate a series of cell-specific laminin reporter (Lam-Rep) mice. Using these Lam-Rep mice,
we will determine the cellular source of laminin in brain BM, estimate their relative abundance, and
characterize the temporary and spatial expression profile of each individual cell type-derived laminin
during normal aging. In Aim 2, cell-specific Lam-Rep mice will be crossed into the 5xFAD background.
The temporary and spatial expression profile of each individual cell-derived laminin in the resulting
Lam-Rep-5xFAD mice and their non-AD Lam-Rep littermates will be determined similarly as described
in Aim 1. Successful completion of this study will fill the gap of knowledge in the field by elucidating the
cellular source of laminin in brain BM and characterizing the temporary/spatial expression profile of
each individual cell type-derived laminin under both normal and AD conditions. These findings will
enable correlation studies between loss of specific cell type-derived laminin and AD pathology; and
may identify unique laminin changes that are useful in early AD diagnosis and prognosis prediction. In
addition, this proposal will also address a critical barrier to progress in the field by generated an
innovative laminin knock-in mouse line, which allows labeling of laminin in a cell-specific and Cre-
dependent manner. This genetic tool is also valuable to researchers in other fields (e.g. in vivo imaging
and leukocyte transmigration). These studies will lead to a breakthrough in laminin/BM research and
substantially move the field forward.

## Key facts

- **NIH application ID:** 10283460
- **Project number:** 1R21AG073862-01
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Yao Yao
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $411,125
- **Award type:** 1
- **Project period:** 2021-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283460

## Citation

> US National Institutes of Health, RePORTER application 10283460, Cell-specific changes of laminin expression in the CNS in Alzheimer’s disease (1R21AG073862-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10283460. Licensed CC0.

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