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Genetic Studies

The Apolipoprotein E e4 (ApoE e4) Phenotype of AD

Phenotype of AD During the past several years, our research group in collaboration with Dr. Joel Gelernter has completed a number of studies to examine phenotypic correlates of the ApoE e4 allele—the major genetic risk factor for AD—in individuals who suffer from probable AD. A highlight of this research has been the finding that AD patients who carry the ApoE e4 allele are at greater risk than non-carriers for developing debilitating psychotic symptoms, particularly as the severity of their dementia progresses (Zdanys et al, Neuropsychopharmacology, 2007).

However, ApoE e4 does not appear to influence the rate of cognitive or functional deterioration in patients with AD (e.g., Kleiman et al, Dement Geriatr Cogn Disord, 2006). Efforts to establish neural substrates for a behavioral ApoE e4 phenotype in AD have thus far yielded unclear results. The structural MRI literature is fairly unified in observing greater medial temporal lobe atrophy in association with the e4 allele in AD (e.g., Basso et al, Neurobiol Aging, 2006). However, functional imaging studies with PET and SPECT have not established a consistent pattern of regional cerebral activity associated with e4 (e.g., van Dyck et al, Arch Neurology, 1998).

We are currently furthering this effort with the new PET ligand, [11C]PIB, to assess amyloid plaques in healthy subjects who are at risk for AD. In a study funded by the Alzheimer’s Association, we are examining whether amyloid burden, as measured using [11C]PIB, is increased in healthy individuals (age 50-65) with a family history of AD who also carry ApoE e4.