Role of apolipoprotein E in the pathogenesis of Alzheimer's disease and molecular mechanisms

Alzheimer's disease (AD), as one severe neurodegenerative disorder, severely threatens public health under the current aging of population. Some studies have speculated the presence of apolipoprotein E (apoE) in the occurrence and progression of AD. This study thus investigated the role of apoE in AD pathogenesis and related molecular mechanisms. Neural tissue samples from both AD model rats and normal rats were collected for quantifying apoE expression levels using RT- PCR and Western blotting. Cultured neural cells D283 were then transfected to over- express apoE or to down- regulate apoE using RNA interference approach. MTT assay and flow cytometry were applied to describe the growth and apoptosis of D283 cells. Clonal formation assay was then used to measure the ability of cell proliferation. AD rats had elevated apoE protein and mRNA levels compared to normal animals. Anti- sense siRNA of apoE inhibited the growth of D283 cells and induce their apoptosis, accompanied with lower clonal formation ability. The over- expression of apoE, on the contrary, facilitated cell growth, inhibited apoptosis, and potentiated clonal formation. ApoE expression level is closely correlated with AD. The lowering of apoE level inhibits neural cell D283 growth and clonal formation while induces cell apoptosis. Over- expression of apoE can facilitate cell growth and proliferation while inhibit apoptosis.