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P3‐271: Association of candidate gene susceptibility alleles on chromosome 10 with Alzheimer's disease risk and endophenotypes
Author(s) -
Walker Louise,
Allen Mariet,
Cox Claire,
Younkin Samuel,
Younkin Linda,
Carrasquillo Minerva,
Zou Fanggeng,
Ma Li,
Kouri Naomi,
Pankratz Ver S.,
Dickson Dennis,
Boeve Bradley,
Petersen Ronald C.,
Graff-Radford Neill R.,
Younkin Steven G.,
Ertekin-Taner Nilufer
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1839
Subject(s) - haplotype , single nucleotide polymorphism , genotype , genetics , allele , snp , biology , endophenotype , apolipoprotein e , gene , disease , medicine , cognition , neuroscience
ogy. Cerebral glucose metabolism is reduced in AD patients with relative sparing of the primary motor and sensory cortices. We studied cerebral glucose metabolism in seven monozygotic (MZ) and nine same-sexed dizygotic (DZ) twin pairs discordant for AD using positron emission tomography (PET). Methods: The results based on manually drawn regions of interest (ROI) of the MZ and DZ twins have been previously published. However, this is the first PET study on twin pairs discordant for AD in which both MZ and DZ twin pairs were studied with identical methodology, which enabled evaluation of the possible genetic vs. environmental contribution to glucose metabolism and susceptibility to develop AD. To obtain objective and explorative results concerning differences in glucose metabolism, the analysis was made utilizing modern voxel-based analysis methodology statistical parametric mapping without a priori hypothesis about the locations of possible differences. To obtain quantification of regional glucose metabolism, an automated ROI analysis was performed. This method eliminates the possibility of observer-induced bias caused by manually drawing the ROIs separately for each subject. Results: We found the cerebral glucose metabolism to be reduced in the demented co-twins compared to controls in cerebral regions affected by AD (reduction ranging from 32 to 7 %, p 0.01-0.15). Also the non-demented MZ co-twins showed reductions in glucose metabolism in parietal (reduction 14 %, p 0.04), lateral temporal (12 %, p 0.02) and medial temporal (7 %, p 0.11) cortices as well as in putamen (13 %, p 0.05). In contrast, no reductions in cerebral GMR were found in the non-demented DZ co-twins. Conclusions: The reductions in non-demented MZ co-twins are possibly early indicators of the disease process before onset of clinical dementia or are genetic markers of susceptibility to AD. As MZ twins have all genes in common, whereas DZ twins share on average half of their segregating genes, the difference between non-demented MZ and DZ co-twins may be due to genetic differences.