APOE and modulation of Alzheimer's and frontotemporal dementia
Kuopio University Hospital, Kuopio, Northern Savo, Finland Neuroscience Letters
(Impact Factor: 2.03).
02/2004; 356(3):167-70. DOI: 10.1016/j.neulet.2003.11.042
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.
Available from: Mario Grassi
- " vulnerability not only in AD but also in FTD and that other concomitant genetic and / or environmental factor ( s ) might modu - late the detrimental effects of APOE E4 leading to the different regional vulnerability that is at the basis of the topographical dif - ferences in the affected areas in AD ( mediotemporal ) and FTD ( frontotemporal ) ( Boccardi et al . , 2004 ) . Taken all this together and based on our own data , APOE might be a locus to be further char - acterized in the Italian FTD population , and conversely , the risk of a contamination of AD cases within our study cohort , if any , is likely to be minimal . The classical association analysis was followed by the SNPs - to - genes analys"
Available from: Philipp G Sämann
- "This evidence prompts the use of brain volume as an intermediate phenotype for association studies of diseaserelated gene variants. Several imaging genetics studies have already confirmed the genetic effects of APOE-4 load on regional brain atrophy (Boccardi et al., 2004; Geroldi et al., 1999; Hashimoto et al., 2001; Lehtovirta et al., 1995, 1996; Tanaka et al., 1998), including a recent study (Filippini et al., 2009) that used the same cohort as we report here. "
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ABSTRACT: Replications of the association between APOE-ε4 allele load and regional brain atrophy in Alzheimer's disease (AD) patients hold promise for future studies testing relationships between other disease risk gene variants and brain structure. A polymorphism, rs10868366, in the Golgi phosphoprotein 2 gene, GOLM1, was recently identified as an AD risk factor in a genome-wide association study. In a subset of the same AD cohort, we used voxel-based morphometry to test for association between the disease risk genotype and reduced regional gray matter (GM) volume in AD patients (n = 72). A mean 14% reduction in GM volume was observed in the left frontal gyrus with the higher risk GG genotype. A similar association was observed in an independent, dataset of nondemented subjects (n = 278), although with a smaller effect (1%). This replicated association with GM structural variation suggests that GOLM1 polymorphisms may be related to cognitive phenotypes. The greater effect size in AD patients also suggests that the GG genotype could be a risk factor for the expression of cognitive deficits in AD.
Available from: Sarah K Madsen
- "Some comparison is warranted between this approach and other methods for hippocampal mapping. Other hippocampal mapping studies by our group have contrasted the atrophy patterns in Lewy Body dementia, vascular dementia (Scher et al., in press), amnestic MCI (Becker et al., 2006), fronto-temporal dementia (Frisoni et al., 2006), and in those at genetic risk for AD (Boccardi et al., 2004) revealing morphometric signatures characteristic of each condition. These prior reports used the same surface parameterization methods and radial distance measures as were used in this report (statistics of radial atrophy), but the studies relied on manual tracing rather than automated segmentation, which greatly accelerates the rate at which scans can be analyzed. "
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ABSTRACT: As one of the earliest structures to degenerate in Alzheimer's disease (AD), the hippocampus is the target of many studies of factors that influence rates of brain degeneration in the elderly. In one of the largest brain mapping studies to date, we mapped the 3D profile of hippocampal degeneration over time in 490 subjects scanned twice with brain MRI over a 1-year interval (980 scans). We examined baseline and 1-year follow-up scans of 97 AD subjects (49 males/48 females), 148 healthy control subjects (75 males/73 females), and 245 subjects with mild cognitive impairment (MCI; 160 males/85 females). We used our previously validated automated segmentation method, based on AdaBoost, to create 3D hippocampal surface models in all 980 scans. Hippocampal volume loss rates increased with worsening diagnosis (normal=0.66%/year; MCI=3.12%/year; AD=5.59%/year), and correlated with both baseline and interval changes in Mini-Mental State Examination (MMSE) scores and global and sum-of-boxes Clinical Dementia Rating scale (CDR) scores. Surface-based statistical maps visualized a selective profile of ongoing atrophy in all three diagnostic groups. Healthy controls carrying the ApoE4 gene atrophied faster than non-carriers, while more educated controls atrophied more slowly; converters from MCI to AD showed faster atrophy than non-converters. Hippocampal loss rates can be rapidly mapped, and they track cognitive decline closely enough to be used as surrogate markers of Alzheimer's disease in drug trials. They also reveal genetically greater atrophy in cognitively intact subjects.
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