APOLIPOPROTEIN-E GENOTYPES IN PRIMARY PROGRESSIVE APHASIA

We obtained apolipoprotein E genotyping in a population of 12 consecut ive patients who fulfilled rigorous criteria for the clinical diagnosi s of primary progressive aphasia (PPA). The allele frequencies were 4% for E2, 83% for E3, and 13% for E4. This pattern of allele distributi on was significantly different from the pattern seen in groups of pati ents either with the clinical diagnosis of probable Alzheimer's diseas e (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 repo rted in populations of patients with PRAD or AD. The E4 allele is ther efore not a significant risk factor for developing PPA. These results provide neurobiological support for the syndromic distinction of PPA f rom 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 h as biological validity in that it identifies a population that is gene tically different from the population of patients with a clinical diag nosis of PRAD.