Apolipoprotein E genotype and hippocampal asymmetry in Alzheimer's disease: a volumetric MRI study

Abstract

Asymmetry of brain structures is common to many species and is even present in utero. Some developmental, pathological, and dementing diseases are associated with alterations in normal anatomical asymmetries. Anatomical asymmetries, however, have been only superficially studied in Alzheimer's disease. Recent evidence indicates that the allele 4 of the apolipoprotein E (ApoE), a well known risk factor for Alzheimer's disease, might play a part in determining some brain morphological changes both in normal carriers and in patients with Alzheimer's disease. This study evaluated the eVect of the ApoE genotype on hippocampal asymmetry in patients with Alzheimer's disease carrying 0, 1, and 2 copies of the allele. Volumetric right-left diVerences of the hippocampi were computed in 28 right handed patients with Alzheimer's disease (14 -/-, 9 4/-, and 5 4/4) and 30 controls without detectable cognitive deficit. In controls, the right hippocampus was larger than the left, whereas in patients with Alzheimer's disease this asymmetry was progressively reduced with increasing gene dose of the 4 allele, and the asymmetry was reversed in the 4/4 Alzheimer's disease group. The mean right-left volume diVerences were: 1.2, 0.7, 0.2, and -1.0 in controls, -/-, 4/-, and 4/4 patients, respectively (sex adjusted p for trend=0.017). The data indicate a dose dependent eVect of the ApoE 4 allele on hippocampal volume asymmetry in Alzheimer's disease. (J Neurol Neurosurg Psychiatry 2000;68:93-96)

Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia

“…One possible explanation for this finding in our study is the inclusion of early age-of-onset AD (age of onset below 65) because these same neocortical regions coincide with areas most severely affected in younger AD patients (24). AD 4 carriers also had more hippocampal atrophy than noncarriers, which is consistent with the majority of existing in vivo neuroimaging studies (19)(20)(21). Although this was not a longitudinal study, apoE 4 dose has also been correlated with the rate of hippocampal atrophy (25).…”

“…Neuroimaging studies mapping brain structural changes associated with apoE in AD have shown an 4 allele dose-effect on hippocampal, amygdalar, and entorhinal cortical atrophy (19)(20)(21). To our knowledge, only one small case series investigated the apoE4 morphologic effect in bvFTD, showing a trend of greater right frontal lobar atrophy in patients carrying the 4 allele (21).…”

Asymmetry in Auditory and Spatial Attention Span in Normal Elderly Genetically At Risk for Alzheimer’s Disease

“…Clues to another possible reason for the inconsistent findings may be derived from neuroimaging studies of elderly subjects at risk for AD. Specifically, neuroimaging results suggest a higher incidence of asymmetric structural and metabolic changes in at-risk individuals (Bigler et al, 2002;Celsis et al, 1997;Geroldi et al, 2000;Small et al, 1995;Soininen, et al, 1994). Such findings would be expected, given that asymmetric neurodegeneration and lateralized cognitive deficits are frequent findings in early AD (Albert, Duffy, & McAnulty, 1990;Demadura, Delis, Jacobson, & Salmon, 2001;Martin, 1990;Massman & Doody, 1996;Strite, Massman, Cooke, & Doody, 1997), with greater verbal/visuospatial asymmetries in the e4 genotype in AD (Finton et al, 2003).…”

MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders

“…116 Alzheimer's disease In Alzheimer's disease (AD) hippocampal volume loss is a hallmark of the disorder. 117,[118][119][120][121][122][123][124][125][126][127][128][129][130] Smaller hippocampal volume is also present in mild AD, 131,132 in African Americans with AD, 133 and is more pronounced in those AD patients who carry the epsilon 4 allele [134][135][136] (for an exception see Bigler et al 137 ). A study comparing mild AD patients with nondemented controls using large-deformation high-dimensional brain mapping found significant volume loss over time and different patterns of hippocampal shape change over time, that distinguished mild AD from healthy aging.…”