Apolipoprotein E and beta-amyloid levels in the hippocampus and frontal cortex of Alzheimer's disease subjects are disease-related and apolipoproteinE genotype dependent

The epsilon 4 allele of apolipoprotein E (apoE) is associated with increase d risk for the development of Alzheimer's disease (AD), possibly due to int eractions with the beta-amyloid (A beta) protein. The mechanism by which th ese two proteins are linked to AD is still unclear. To further assess: thei r potential relationship with the disease, we have determined levels of apo E and A beta isoforms from three brain regions of neuropathologically confi rmed AD and non-AD tissue. In two brain regions affected by AD neuropatholo gy, the hippocampus and frontal cortex, apoE levels were found to be decrea sed while A beta(1-40) levels were increased. Levels of apoE were unchanged in AD cerebellum. Furthermore, levels of apoE and A beta(1-40) were found to be apoE genotype:dependent, with lowest levels of apoE and highest level s of A beta(1-40) occurring in epsilon 4 allele carriers. These results sug gest that reduction in apoE levels may give rise to increased deposition of amyloid peptides in AD brain. (C) 1999 Published by Elsevier Science B.V. All rights reserved.