APOE deficiency inhibits amyloid-facilitated (A) tau pathology (T) and neurodegeneration (N), halting progressive ATN pathology in a preclinical model.

ABSTRACT: In AD, amyloid pathology (A) precedes progressive development of tau pathology (T) and neurodegeneration (N), with the latter (T/N) processes associated with symptom progression. Recent anti-amyloid beta (Aβ) clinical trials raise hope but indicate the need for multi-targeted therapies, to effectively halt clinical AD and ATN pathology progression. APOE-related putative protective mutations (including APOE3Christchurch, RELN-COLBOS) were recently identified in case reports with exceptionally high resilience to autosomal dominant AD. In these cases, Nature provided proof of concept for halting autosomal dominant AD and ATN progression in humans, despite a high amyloid load, and pointing to the APOE pathway as a potential target. This is further supported by the recent identification of APOE

SUBMITTER: Vanherle S 

PROVIDER: S-EPMC12436195 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature