Multi-transcriptomics Reveals Brain Cellular Responses to Peripheral Infection in Alzheimer's Disease Model Mice

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2023 Jul 12

PMID 37436901

Authors

Yi Lu

Carolina Saibro-Girardi

Nicholas Francis Fitz

Mikayla Ranae McGuire

Mary Ann Ostach

A N M Mamun-Or-Rashid

Iliya Lefterov

Radosveta Koldamova

Affiliations

Soon will be listed here.

Abstract

Peripheral inflammation has been linked to various neurodegenerative disorders, including Alzheimer's disease (AD). Here we perform bulk, single-cell, and spatial transcriptomics in APP/PS1 mice intranasally exposed to Staphylococcus aureus to determine how low-grade peripheral infection affects brain transcriptomics and AD-like pathology. Chronic exposure led to increased amyloid plaque burden and plaque-associated microglia, significantly affecting the transcription of brain barrier-associated cells, which resulted in barrier leakage. We reveal cell-type- and spatial-specific transcriptional changes related to brain barrier function and neuroinflammation during the acute infection. Both acute and chronic exposure led to brain macrophage-associated responses and detrimental effects in neuronal transcriptomics. Finally, we identify unique transcriptional responses at the amyloid plaque niches following acute infection characterized by higher disease-associated microglia gene expression and a larger effect on astrocytic or macrophage-associated genes, which could facilitate amyloid and related pathologies. Our findings provide important insights into the mechanisms linking peripheral inflammation to AD pathology.

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