[Apolipoprotein E4 and late-onset Alzheimer's disease].
Apolipoprotein E [APOE for protein; APOE for gene] is a 34 kDa plasma protein involved in cholesterol transport. In addition to hepatic cells, glial cells in the nervous system also produce APOE, which is postulated to be involved in the growth and repair of the nervous system during development or after injury. The APOE immunoreactivity was associated with amyloid both in senile plaques and cerebral blood vessels and neurofibrillary tangles (NFTs) in Alzheimer's disease (AD). The immunoreactivity was also found in amyloid of kuru plaques in Creutzfeldt-Jakob disease and other types of cerebral and systemic amyloid. Three common genetic variants of APOE result from different alleles coding for proteins with single amino acid substitutions. The APOE alleles are designated epsilon 4 (Cys 112-->Arg), epsilon 3 (Cys at amino acid 112) and epsilon 4 (Arg 158-->Cys) [E4, E3 and E2 for proteins, respectively]. The APOE-epsilon 4 allele was genetically associated with late-onset familial and sporadic forms of AD as well as with early-onset AD. Protective effect of APOE-epsilon 2 allele for late-onset AD was also reported. APOE was found to be able to bind synthetic amyloid beta peptide (A beta), the primary constituent of senile plaque and cerebrovascular amyloid, forming a complex that resisted dissociation by boiling in SDS. The binding of A beta to APOE-E4 was much more rapid than to APOE-E3. APOE-E3 was also shown to bind to tau, the major component of NFTs, presumably protecting tau from abnormal phosphorylation and slowing the formation of NFTs.(ABSTRACT TRUNCATED AT 250 WORDS)