Accumulated BCAAs and BCKAs contribute to the HFD-induced deterioration of Alzheimer's disease via a dysfunctional TREM2-related reduction in microglial β-amyloid clearance.

ABSTRACT: A high-fat diet (HFD) induces obesity and insulin resistance, which may exacerbate amyloid-β peptide (Aβ) pathology during Alzheimer's disease (AD) progression. Branched-chain amino acids (BCAAs) accumulate in obese or insulin-resistant patients and animal models. However, roles of accumulated BCAAs and their metabolites, branched-chain keto acids (BCKAs), in the HFD-induced deterioration of AD and the underlying mechanisms remains largely unclear. In this study, APPswe/PSEN1dE9 (APP/PS1) transgenic mice were fed a HFD for 6 months, and the BCAAs content of the HFD was adjusted to 200% or 50% to determine the effects of BCAAs. The HFD-fed APP/PS1 mice accumulated BCAAs and BCKAs in the serum and cortex, which was accompanied by more severe cognitive deficits and AD-related pathology. The a

SUBMITTER: Yang Y 

PROVIDER: S-EPMC11667870 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature