ALZHEIMER'S RESEARCH & THERAPY_APOE WMH VBM in AD_2015.pdf (original) (raw)
Related papers
ALZHEIMER'S RESEARCH & THERAPY_APOE WMH VBM_2015.pdf
Introduction: White matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer's disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD.
The ε4 genotype of apolipoprotein E and white matter integrity in Alzheimer's disease
Alzheimer's & Dementia, 2013
Background: In this multicenter study, we investigated a possible association between the APOE ε4 allele and white matter (WM) integrity in Alzheimer's disease (AD) using diffusion tensor imaging (DTI). Methods: We analyzed fractional anisotropy (FA) and mean diffusivity (MD) as indices of WM integrity in 70 AD patients (35 APOE ε4 carriers, 35 noncarriers) and 56 healthy control (HC) subjects (28 APOE ε4 carriers, 28 noncarriers). APOE ε4 carriers and noncarriers were matched for age and gender within each diagnostic group. Results: We found significant effects of diagnosis (P corrected , .05 [FWE]; i.e., smaller FA values and larger MD values in AD patients compared with HCs) and significant effects (P , .001) of APOE ε4 carrier status on MD in HCs but not in AD subjects.
Dementia, quantitative neuroimaging, and apolipoprotein E genotype
AJNR. American journal of neuroradiology
Quantitative MR imaging differences in an elderly population of subjects with various clinical disorders (including dementia, particularly Alzheimer's disease and vascular dementia) and disorders of mild cognitive impairment were examined. Potential quantitative MR differences were assessed by presence or absence of the apolipoprotein E (APOE) epsilon4 allele and by level of cognitive deficit. One hundred eighty subjects with a diagnosis of dementia or other clinical disorders were identified from an eligible population of 5,677 elderly individuals. Age, duration of disease, and head size (where appropriate) were considered as covariates. APOE genotype was determined by polymerase chain reaction using buccal material. Axial and coronal intermediate- and T2-weighted MR images were quantified using a multispectral segmentation algorithm. Cognitive status was assessed by means of a modified Mini-Mental Status Examination. All types of dementing illness showed significant volume red...
Altered brain white matter integrity in healthy carriers of the APOE 4 allele: A risk for AD?
Neurology, 2006
Background: Previous research has shown that polymorphisms of apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood. Methods: The authors used diffusion tensor imaging to investigate ultrastructural properties in brain white matter to detect pathologic processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE ε3 allele, 10 were homozygous for the APOE ε4 allele, and 20 had the APOE ε34 allele combination. All individuals were nondemented, and the groups were matched on demographic variables and cognitive performance. Results: The results showed a decline in fractional anisotropy, a marker for white matter integrity, in the posterior corpus callosum of ε4 carriers compared to non-carriers. Additional sites of altered white matter integrity included the medial temporal lobe. Conclusions: Although the mechanism underlying vulnerability of white matter tracts in APOE ε4 carriers is still unknown, these findings suggest that increased genetic risk for developing Alzheimer disease is associated with changes in microscopic white matter integrity well before the onset of dementia.
Alzheimer's & Dementia, 2014
Background-We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase risk for Alzheimer's disease (AD). Here, we examined whether individuals with APOE*4have increased parietal WMH volume. Methods-Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n=694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n=539, 8 with dementia) in Montpellier. The
The influence of Apolipoprotein E genotype on regional pathology in Alzheimer’s disease
BMC Neurology, 2013
Background: Carriers of the ApoE ε4 allele are at a greater risk for developing Alzheimer's disease (AD) and those who do develop AD tend to have a much greater neuropathological disease burden. Although several studies have shown significant differences in AD pathology among ε4 carriers and non-carriers, few have characterized these differences in terms of brain region and neuropathological score frequency. Methods: 566 pathologically-confirmed AD cases who were followed prospectively with antemortem dementia diagnoses (312 ApoE ε4 carriers and 254 ApoE ε4 non-carriers) were compared on the frequencies of neuropathological frequency scores (none, sparse, moderate, frequent) among several different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal) using the CERAD scoring system. Pathology score frequencies were analyzed by carrier status (ε4 carrier vs. ε4 non-carrier) and by genotype (2/3, 3/3, 2/4, 3/4, 4/4). Both analyses investigated pathology score frequencies among different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal). Results: ε4 carriers had a significantly lower age at death (p <0.001) and significantly higher Braak scores (p <0.001) than ε4 non-carriers. Genotype comparison revealed that plaque and tangle pathologies increased in the following pattern, 2/3<3/3<2/4<3/4<4/4, for several brain regions. When stratified by age and ApoE ε4 carrier status, ε4 carriers tended to have significantly more frequent scores across most cortical areas. However, non-carriers age 90 and older tended to have greater plaque pathology than carriers. For tangle pathology, ε4 carriers tended to have significantly more "frequent" scores than non-carriers, except for the hippocampal and entorhinal areas in individuals age 90 and older. Conclusions: ApoE ε4 carriers had a significantly higher percentage of "frequent" scores for plaques and tangles when compared to ApoE ε4 non-carriers for several brain regions. However, ε4 non-carriers age 90 and older tended to have less plaque and tangle pathology in certain brain regions. These results demonstrate that AD pathology may manifest itself differently based on ApoE genotype and suggest that ApoE carriers and non-carriers may have different patterns of AD neuropathology location and density.