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

Identification of endogenous pathological amyloid beta peptides (A beta) forms in the brains of patients with Alzheimer's disease (AD) is still unclear. In healthy brain, A beta 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 A beta and their interaction with the ApoE fragments in post-mortem brains from control and AD patients by western blots and co-immunoprecipitation. Three A beta-containing peptides and three ApoE fragments were specifically found in the brain of AD patients. Co-immunoprecipitations showed that ApoE fragments and A beta 1-42 peptides are co-partners in heteromers of 18 and 16 kDa while ApoE-fragments and A beta peptides of 12 kDa did not interact with each other. Formation of the 18 kDa ApoE-fragment/A beta heteromers is specifically increased in ApoE4 carriers and is a strong brain marker of AD while 16 kDa ApoE-fragment/A beta and A beta 12 kDa correlate to memory deficit. These data show that in patients with AD, ApoE fragmentation generates peptides that trap A beta in the brain. Inhibiting the fragmentation or targeting ApoE fragments could be exploited to define strategies to detect or reverse AD.