Lipoproteins in clinical laboratory medicine]

The characteristics and metabolism of lipoproteins were reviewed. Apolipoproteins has been studied in the fields of neurological diseases as well as hyperlipidemia. A highly significant association between apolipoprotein E (ApoE) epsilone 4 allele and late-onset familial and sporadic Alzheimer's disease (AD) was reported. The recent studies also described the following: (1) late-onset familial AD linked to the proximal long arm of chromosome 19; (2) the presence in the CSF of several proteins, one of which was ApoE, what bound to immobilized amyloid beta-peptide (beta A4) with high avidity; and (3) staining by antisera to ApoE of senile plaques, neurofibrillary tangles, and cerebral vessel amyloid deposits in AD brains. Furthermore, (4) both purified ApoE isomers, ApoE3 and ApoE4, bound to beta A4 synthetic peptide, forming a complex that resisted dissociation by boiling in sodium dodecyl sulfate, but the isomers showed different kinetics in doing so: binding by ApoE4 was observed in minutes, while binding by ApoE3 required hours; and (5) ApoE4 did not bind to beta A4 peptide at pH less than 6.6, while ApoE3 bound to beta A4 peptide from pH7.6 to 4.6. We studied ApoE phenotype expression and the corresponding allele frequencies (epsilon 2, epsilon 3 and epsilon 4) in Japanese patients with late-onset sporadic AD. The frequency of the ApoE epsilon 4 allele was obviously high in AD patients compared with the controls, but it was not different between vascular dementia patients and the controls. These results suggest that ApoE isoforms may play a functional role in the pathophysiology of late-onset familial and sporadic AD and that the isoform-specific difference in beta A4 binding may be involved in forming the AD lesion.