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Abstract
We obtained apolipoprotein E genotyping in a population of 12 consecutive patients who fulfilled rigorous criteria for the clinical diagnosis of primary progressive aphasia (PPA). The allele frequencies were 4% for E2, 83% for E3, and 13% for E4. This pattern of allele distribution was significantly different from the pattern seen in groups of patients either with the clinical diagnosis of probable Alzheimer's (PRAD) or the histopathologic diagnosis of Alzheimer's disease (AD). The E4 allele frequency in the group of patients with PPA was in the range seen in control populations and was much lower than the one reported in populations of patients with PRAD or AD. The E4 allele is therefore not a significant risk factor for developing PPA. These results provide neurobiological support for the syndromic distinction of PPA from PRAD and are in keeping with neuropathologic evidence showing that the vast majority of patients with PPA do not have the histopathology of AD. Although we do not yet have neuropathologic information on our patients, these results indicate that the clinical diagnosis of PPA has biological validity in that it identifies a population that is genetically different from the population of patients with a clinical diagnosis of PRAD.
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