PXD055552

PXD055552 is an original dataset announced via ProteomeXchange.

Title	Chronic alcohol exposure during young adulthood attenuates microglial reactivity and downstream immune response pathways in a mouse model of tauopathy later in life
Description	Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by the buildup of amyloid-β and tau protein tangles. Alcohol use has been identified as a risk factor for AD; however, the molecular mechanisms underlying this potential causal link remain elusive. An emerging area of research focuses on the role of microglia, the brain's innate immune cells, in AD pathogenesis, with evidence suggesting that alcohol exposure may prime microglia to exhibit an exaggerated immune response when they are subsequently exposed to proinflammatory stimuli. We used a single 10-day chronic-plus-binge alcohol exposure model in male and female C57BL/J mice aged 8- to 10-weeks old. One month later, tauopathy was induced via adenoviral vector (AAV)-mediated overexpression of h-p301L tau. After 2.5 months, the mice underwent behavioral and cognitive testing. Two weeks later, microglia were collected using fluorescence-activated cell sorting (FACS) and processed for unbiased mass spectrometry and deep proteomic analysis to determine the molecular pathways related to microglial reactivity. Microglia from mice exposed to alcohol in young adulthood exhibited a blunted immune response when challenged with AAV-mediated delivery and accumulation of human tau later in life. This was characterized by decreased expression of MHC II- and interferon-associated proteins and bioinformatic prediction of inhibited inflammation-related pathways in the absence of gross histological, behavioral, or cognitive deficits. These results demonstrate unique, temporally specific microglial reactivity to tau that is modulated by early life alcohol exposure, implicating a microglial response that could negatively affect the mechanisms necessary for tau clearance and potentially exacerbate tau pathogenesis. This study provides novel insights into the long-term effects of early alcohol exposure on microglial function and the complexity of context-dependent microglial involvement in tau pathology. Consideration of early life environmental factors is critical for understanding and potentially mitigating the risk of neurodegenerative diseases, such as AD.
HostingRepository	PRIDE
AnnounceDate	2025-03-31
AnnouncementXML	Submission_2025-03-31_12:22:55.159.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stanley Stevens
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-04 09:27:51	ID requested
⏵ 1	2025-03-31 12:22:55	announced

10.1111/ACER.70034;

submitter keyword: microglia

alcohol

proteomics

tauopathy

Alzheimer’s disease

Stanley Stanley
contact affiliation	University of South Florida
contact email	smstevens@usf.edu
lab head
Stanley Stevens
contact affiliation	University of South Florida
contact email	smstevens@usf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055552
     1. Label: PRIDE project
     2. Name: Chronic alcohol exposure during young adulthood attenuates microglial reactivity and downstream immune response pathways in a mouse model of tauopathy later in life