APOE and modulation of Alzheimer's and frontotemporal dementia.
ABSTRACT To investigate the difference in the morphologic expression of frontotemporal dementia (FTD) and Alzheimer's disease (AD) in patients carrying and not carrying the epsilon4 allele of APOE, MR images of 26 controls, 18 AD patients (11 carrying the epsilon4 allele, seven non-carriers), and eight FTD (two carriers, six non-carriers) were compared using voxel by voxel analysis. Greater atrophy was found in the disease-specific regions of the epsilon4 carriers vs the non-carriers at P < 0.05 corrected: medial temporal atrophy was greater in the AD carrying the epsilon4 allele, right ventral striatal atrophy in the FTD carrying the allele. The non-carriers did not have atrophic regions compared to the carriers. The epsilon4 allele of the APOE might modulate the expression of degenerative dementias by enhancing the specific effects of neurodegenerative diseases on the brain.
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ABSTRACT: Apolipoprotein ε4 (apoE4) has been strongly linked with Alzheimer's disease (AD) and contributes to several other neurological disorders. We investigated the influence of ε4 allele carrier status on the pattern of gray matter atrophy and disease severity in 51 patients with probable AD and 31 patients with behavioral variant frontotemporal dementia (bvFTD), compared with 56 healthy controls. Voxel-based morphometry was performed by using statistical parametric mapping. The ε4 allele frequency was higher in the AD group (P < 0.001) than the controls but not in the bvFTD group. No differences in demographic or cognitive profiles were observed between ε4 allele carriers and noncarriers within any of the diagnostic groups. However, ε4 carrier status was associated with more severe brain atrophy in disease-specific regions compared with noncarriers in both AD and bvFTD. AD ε4 carriers showed greater atrophy in the bilateral parietal cortex and right hippocampus, and bvFTD ε4 carriers demonstrated greater atrophy in the bilateral medial, dorsolateral, and orbital frontal cortex, anterior insula, and cingulate cortex with right predominance. This regional ε4 effect is consistent with the hypothesis that apoE may affect the morphologic expression uniquely in different neurodegenerative diseases. The atrophy patterns in ε4 carriers may indicate that they are at greater risk for clinical progression.Proceedings of the National Academy of Sciences 02/2009; 106(6):2018-2022. · 9.81 Impact Factor
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ABSTRACT: OBJECTIVE: Case-control studies have not been consistent in showing association between apolipoprotein E (APOE) polymorphisms and frontotemporal lobar degeneration (FTLD), producing contradictory findings. The study objective was to define and quantify further the disease risk associated with the carriage of different APOE alleles to determine whether APOE gene polymorphism is a risk factor for FTLD. METHODS: A systematic review of all case-control studies investigating the association between the APOE gene and FTLD up to December 2011 was conducted. Case-control studies using clinical or pathological criteria for FTLD and reporting APOE allelic or genotypic data were included. Pooled odds ratios (ORs) were estimated using a random effects model, and 95% confidence intervals (CIs) were calculated. RESULTS: Twenty-eight case-control studies met the inclusion criteria. Carriage of the ε2 allele had no effect on disease risk. On the contrary, carriage of the ε4 allele was associated with a significantly increased disease risk (ε4 carriers vs non-ε4 carriers: OR, 1.94; 95% CI, 1.43-2.64; ε4 vs ε3 allele: OR, 1.83; 95% CI, 1.34-2.52). Furthermore, a gene-dosage effect for the ε4 allele was found. There was no evidence of publication bias, but heterogeneity between the studies was high. CONCLUSIONS: Our study provides evidence for an association between the APOE ε4 allele and frontotemporal lobar degeneration.Alzheimer's & dementia: the journal of the Alzheimer's Association 05/2013; · 14.48 Impact Factor