Functional correlates of Apolipoprotein E genotype in Frontotemporal Lobar Degeneration

Barbara Borroni,Giuseppe Bellelli,Monica Di Luca,Chiara Agosti,Alessandro Padovani,Silvana Archetti,Daniela Perani,Barbara Paghera

doi:10.1186/1471-2377-6-31

Abstract

BackgroundIt 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 ε4 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.MethodsFifty-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.ResultsApoE genotype influenced both clinical and functional features in FTLD. ApoE ε4-carriers were more impaired in long-term memory function (ApoE ε4 vs. ApoE non ε4, 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).ConclusionThe 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.

Highlights

It has been recently demonstrated that in Frontotemporal Lobar Degeneration (FTLD) memory deficits at presentation are commoner than previously thought
The present findings support the view that Apolipoprotein E (ApoE) genotype might be considered a disease-modifying factor in FTLD, contributing to define a specific clinical presentation, and might be of relevance for pharmacological approaches
It has been demonstrated that ApoE genotype modulates cerebral perfusion in late middle-age cognitively normal subjects, ApoE ε4 homozygous having reduced glucose metabolism in the same regions involved in Alzheimer Disease (AD) [4]

Summary

Introduction

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. It has been demonstrated that ApoE genotype modulates cerebral perfusion in late middle-age cognitively normal subjects, ApoE ε4 homozygous having reduced glucose metabolism in the same regions involved in AD [4]. Based on these observations, we hypothesised that ApoE genotype might play a key-role in influencing the cerebral functional pattern as well as the degree of memory deficits in FTLD patients. FTLD patients were enrolled, ApoE genotype defined, and neuropsychological standardized assessment as well as Single Photon Emission Tomography (SPECT) cerebral perfusion patterns assessed

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