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Multi-transcriptomics reveals brain cellular responses to peripheral infection in Alzheimer's disease model mice.


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.

SUBMITTER: Lu Y 

PROVIDER: S-EPMC10530196 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Multi-transcriptomics reveals brain cellular responses to peripheral infection in Alzheimer's disease model mice.

Lu Yi Y   Saibro-Girardi Carolina C   Fitz Nicholas Francis NF   McGuire Mikayla Ranae MR   Ostach Mary Ann MA   Mamun-Or-Rashid A N M ANM   Lefterov Iliya I   Koldamova Radosveta R  

Cell reports 20230711 7


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  ...[more]

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