Soluble cerebral Aβ protofibrils link Aβ plaque pathology to changes in CSF Aβ₄₂/Aβ₄₀ ratios, neurofilament light and tau in Alzheimer's disease model mice.

ABSTRACT: The Aβ₄₂/Aβ₄₀ ratio in the cerebrospinal fluid (CSF) and the concentrations of neurofilament light (NfL) and total tau (t-tau) are changed in the early stages of Alzheimer's disease (AD)¹, but their neurobiological correlates are not entirely understood. Here, we used 5xFAD transgenic mice to investigate the associations between these CSF biomarkers and measures of cerebral Aβ, including Aβ₄₂/Aβ₄₀ ratios in plaques, insoluble fibrillar deposits and soluble protofibrils. A high Aβ₄₂/Aβ₄₀ ratio in soluble protofibrils was the strongest independent predictor of low CSF Aβ₄₂/Aβ₄₀ ratios and high CSF NfL and t-tau concentrations when compared to Aβ₄₂/Aβ₄₀ ratios in plaques an

SUBMITTER: Andersson E 

PROVIDER: S-EPMC11922755 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature