P1-268: Apolipoprotein E genotype in biparietal Alzheimer’s disease

Abstract

Patients with Alzheimer's disease (AD) typically present with memory failure. However, some patients present with parietal lobe dysfunction with relatively spared memory: so–called biparietal AD. Such patients often have early age at onset and posterior cortical atrophy on imaging. To investigate the frequency of APOE ϵ4 in biparietal AD. Thirty–nine patients with sporadic AD underwent clinical assessment and investigation, including MRI. Neuropsychological testing was performed using graded–difficulty tests of verbal and visual recognition memory and parietal lobe function. Patients scoring <5th percentile on dominant parietal lobe testing, <5th percentile on at least one test of non–dominant parietal lobe function, and ≥10th percentile on the combined verbal and visual memory tests were defined as biparietal AD; others were classified as typical AD. APOE genotype was determined using standard techniques. We compared the frequency of APOE ϵ4 positive genotype, using Fisher's exact test and clinical characteristics between groups using unpaired t tests. Ten patients fulfilled criteria for biparietal AD; seven had posterior cortical atrophy on MRI. There were no gender, handedness or disease duration differences between the groups. Biparietal patients were younger at symptom onset (56.1±4.1 vs 65.6±6.9; P<0.001), scored higher on the MMSE (23.1±2.8 vs 19.2±4.3; P=0.01) and were less likely to be APOE ϵ4–positive (2/10 vs 25/29, P<.0001). Four biparietal and 29 patients with typical AD had serial volumetric imaging performed one year apart. We found some evidence to suggest that biparietal patients had excess rates of whole brain atrophy compared to patients with typical disease. Despite having younger age at onset, patients with biparietal AD are less likely to be APOE ϵ4–positive. We suggest that in these patients, at least in part mediated by lack of APOE ϵ4, the pathological process is directed away from medial temporal structures and toward the parietal lobes. If replicated in larger studies, this finding may have implications for our understanding of the pathogenesis of AD and factors influencing the regional predilection of this and other neurodegenerative diseases.