Functional correlates of Apolipoprotein E genotype in Frontotemporal Lobar Degeneration

Background: It has been recently demonstrated that in Frontotemporal Lobar Degeneration (FTLD) memory deficits at presentation are commoner than previously thought. Apolipoprotein E ( ApoE) genotype, the major genetic risk factor in sporadic late-onset Alzheimer Disease ( AD), modulates cerebral perfusion in late middle-age cognitively normal subjects. ApoE epsilon 4 homozygous have reduced glucose metabolism in the same regions involved in AD. The aim of this study was to determine whether ApoE genotype might play a key-role in influencing the cerebral functional pattern as well as the degree of memory deficits in FTLD patients. Methods: Fifty-two unrelated FTLD patients entered the study and underwent a somatic and neurological evaluation, laboratory examinations, a brain structural imaging study, and a brain functional Single Photon Emission Tomography study. ApoE genotype was determined. Results: ApoE genotype influenced both clinical and functional features in FTLD. ApoE epsilon 4-carriers were more impaired in long-term memory function (ApoE epsilon 4 vs. ApoE non epsilon 4, 6.3 +/- 3.9 vs. 10.1 +/- 4.2, p = 0.004) and more hypoperfused in uncus and parahippocampal regions ( x, y, z = 38,- 6,- 20, T = 2.82, cluster size = 100 voxels; - 32,- 12,- 28, T = 2.77, cluster size = 40 voxels). Conclusion: The present findings support the view that ApoE genotype might be considered a disease-modifying factor in FTLD, thus contributing to define a specific clinical presentation, and might be of relevance for pharmacological approaches.