Cell type-specific contributions to impaired blood-brain barrier and cerebral metabolism in presymptomatic 5XFAD mice.

ABSTRACT: Altered cerebral metabolism and blood-brain barrier (BBB) dysfunction are emerging as critical contributors to the preclinical phase of Alzheimer's disease (AD), underscoring their role in early pathogenesis. To identify sensitive biomarkers before irreversible neuronal loss and cognitive decline, we examined 5XFAD mice at 3 months of age by applying multiple advanced MRI techniques. Arterial spin tagging based MRI revealed increased BBB permeability and water extraction fraction, indicating compromised BBB integrity at the early stage of pathogenesis in 5×FAD mice. Despite preserved cerebral blood flow, a decreased unit mass cerebral metabolic rate of oxygen (CMRO₂) was evident in the same cohorts of 5XFAD mice. Interestingly, a region-specific decrease of tissue pH values was

SUBMITTER: Yao M 

PROVIDER: S-EPMC12240590 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature