Late-onset familial Alzheimer disease (LOFAD) is a genetically heterogeneous and complex disease for which only one locus, APOE, has been definitively identified.
We analyzed at the molecular level with presenilin-1 (PS-1) and apolipoprotein E (apoE) genotyping the affected subjects and asymptomatic relatives of an Italian family with several members affected by late-onset familial Alzheimer's disease (AD).
Apolipoprotein E (apo E) epsilon4 is a risk factor for sporadic and late-onset familial Alzheimer's disease, but it is not well known whether the apo E is associated with spinocerebellar degeneration.
Population studies have established that one of the common isoforms of apolipoprotein E, the apoE4, is associated with higher incidence and earlier age of onset of late onset familial Alzheimer's disease (AD), whereas apoE2 may have the opposite effect.
Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein.
The most dramatic and unexpected finding in this regard was made in early 1993, when it was reported that the presence of the APOE*4 allele is a significant risk factor for the development of late-onset familial Alzheimer's disease, a debilitating brain disorder.
Results showed that > 80% of apoE4-negative AD patients showed marked improvement after 30 weeks as measured by the AD assessment scale (ADAS), whereas 60% of apoE4 carriers had ADAS scores that were worse compared to baseline.
ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon 4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.