Brain regional correlation of amyloid-? with synapses and apolipoprotein E in non-demented individuals: potential mechanisms underlying regional vulnerability to amyloid-? accumulation.

ABSTRACT: To reveal the underlying mechanisms responsible for the regional vulnerability to amyloid-? (A?) accumulation prior to the development of Alzheimer's disease, we studied distribution of A?, apolipoprotein E (apoE), synaptic markers, and other molecules involved in A? metabolism in multiple brain areas of non-demented individuals. Twelve brain regions including neocortical, limbic, and subcortical areas were dissected from brains of non-demented individuals and extracted according to increasing insolubility by a sequential three-step method. The levels of A?40, A?42, apoE, APP, APP-CTF?, BACE1, presenilin-1, neprilysin, insulysin, LRP1, LDLR, synaptophysin, PSD95, GFAP, and lactate were determined by ELISAs or enzymatic assays. The regional distribution of apoE showed moderate-to-strong inverse correlation with levels of A?, especially insoluble A?40. On the other hand, the regional distributions of synaptic markers, particularly PSD95, showed moderate-to-strong positive correlation with levels of A?, especially soluble A?40. The regional correlations between A? and LRP1, GFAP, or lactate were mild-to-moderate. Moderate-to-strong positive regional correlations were observed between apoE and GFAP or lactate and between PSD95 and LRP1. No significant regional correlations were detected between A? and APP, APP-CTF?, BACE1, or presenilin-1, those involved in A? production. There were no significant negative regional correlations between A? and two major A? degrading enzymes, neprilysin and insulysin. These regional correlations remained consistent regardless of the degree of A? accumulation. The regional vulnerability to A? accumulation may be due to a net balance between two competing processes: (1) synapses involved in promoting the initial A? accumulation and (2) astrocyte-derived apoE involved in preventing A? accumulation.

SUBMITTER: Shinohara M 

PROVIDER: S-EPMC3612369 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature