Apolipoprotein e acts at pre-synaptic sites... among others

摘要

It has been practically 20 years since polymorphisms in the apolipoprotein E gene (APOE) were first linked to the risk for developing Alzheimer's disease. And like so many other aspects of this disorder, the mechanistic explanation for this link remains a mystery. One thing is clear, however, individuals carrying an APOE s4 allele have a higher rate of Alzheimer's disease and greater accumulations of amyloid beta-peptide (Abeta), the molecular species increasingly indicted as the key perpetrator of Alzheimer's pathogenesis. However, evidence indicates that APOE genotype may alter neurophysiology and biochemistry independently of A[3 production or accumulation. Differences in neurological activity detected by fMRI and fluorodeoxyglucose (fDG)-PET are associated with possession of an APOE s4 allele in undemented older subjects and in those too young to have significant Abeta accumulation (Bookheimer and Burggren 2009).