ApoE-fragment/Aβ heteromers in the brain of patients with Alzheimer’s disease

Identification of endogenous pathological amyloid β peptides (Aβ) forms in the brains of patients with Alzheimer’s disease (AD) is still unclear. In healthy brain, Aβ can associate with Apolipoprotein E (ApoE) which is involved in its metabolism and clearance. In the brain of patients with AD, ApoE is cleaved and produces ApoE fragments. We studied the forms of Aβ and their interaction with the ApoE fragments in post-mortem brains from control and AD patients by western blots and co-immunoprecipitation. Three Aβ-containing peptides and three ApoE fragments were specifically found in the brain of AD patients. Co-immunoprecipitations showed that ApoE fragments and Aβ1–42 peptides are co-partners in heteromers of 18 and 16 kDa while ApoE-fragments and Aβ peptides of 12 kDa did not interact with each other. Formation of the 18 kDa ApoE-fragment/Aβ heteromers is specifically increased in ApoE4 carriers and is a strong brain marker of AD while 16 kDa ApoE-fragment/Aβ and Aβ 12 kDa correlate to memory deficit. These data show that in patients with AD, ApoE fragmentation generates peptides that trap Aβ in the brain. Inhibiting the fragmentation or targeting ApoE fragments could be exploited to define strategies to detect or reverse AD.