ABSTRACT
The apolipoprotein E (apoE) genotype is the single most important genetic risk factor identified so far for sporadic Alzheimer’s disease (AD). The presence of the ε4 allele, confers a much greater risk of AD compared with the more common ε3 allele and may also be implicated in other degenerative diseases. If the ε2 allele is the basis of comparison, apoE may account for the vast majority of AD risk. The initial discovery of this risk factor a decade ago has since been replicated in numerous laboratories. However, remarkably little progress has been made in understanding how apoE confers increased risk of AD or other diseases. Although the role of apoE in AD is widely assumed to be indirect, through modification of amyloid deposition or clearance, there is also evidence that it may make a direct contribution to neuropathology. Elucidation of the physiological role of apoE in the central nervous system (CNS) and its contribution to neurodegenerative disease should clarify the suitability of apoE as a novel therapeutic target in AD.
