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A CYP46 T/C SNP modulates parahippocampal and hippocampal morphology in young subjects


Hänggi, Jürgen; Mondadori, C R; Buchmann, A (2011). A CYP46 T/C SNP modulates parahippocampal and hippocampal morphology in young subjects. Neurobiology of Aging, 32(6):1023-1032.

Abstract

There is evidence that brain cholesterol metabolism modulates the vulnerability for Alzheimer's disease (AD). Previous data showed that brain beta-amyloid load in elderly subjects with the CYP46 (cholesterol 24S-hydroxylase) TT-positive genotype was higher than in CYP46 TT-negative elderly subjects. We investigated effects of the CYP46 T/C polymorphism on parahippocampal and hippocampal grey matter (GM) morphology in 81 young subjects using structural magnetic resonance imaging based morphometry. We found that young TT-homozygotes exhibited smallest and CC-homozygotes largest parahippocampal and hippocampal GM volumes with the volumes of the CT-heterozygotes ranging in between. Parahippocampal and hippocampal volumes were positively correlated with delayed memory performance in C-carriers and negatively with immediate memory performance in TT-homozygotes. It has been shown that the brain cholesterol metabolism in general modulates dendrite outgrowth, synaptogenesis, and neuron survival, and it was suggested that CYP46 indirectly influences beta-amyloid metabolism. CYP46 C-carriers are privileged both in terms of beta-amyloid metabolism and in terms of brain reserve due to their larger parahippocampal and hippocampal structures. The exact cellular mechanisms that translate the CYP46 allelic variation into volumetric brain differences in the parahippocampal gyrus and hippocampus are still unknown and need to be further investigated.

There is evidence that brain cholesterol metabolism modulates the vulnerability for Alzheimer's disease (AD). Previous data showed that brain beta-amyloid load in elderly subjects with the CYP46 (cholesterol 24S-hydroxylase) TT-positive genotype was higher than in CYP46 TT-negative elderly subjects. We investigated effects of the CYP46 T/C polymorphism on parahippocampal and hippocampal grey matter (GM) morphology in 81 young subjects using structural magnetic resonance imaging based morphometry. We found that young TT-homozygotes exhibited smallest and CC-homozygotes largest parahippocampal and hippocampal GM volumes with the volumes of the CT-heterozygotes ranging in between. Parahippocampal and hippocampal volumes were positively correlated with delayed memory performance in C-carriers and negatively with immediate memory performance in TT-homozygotes. It has been shown that the brain cholesterol metabolism in general modulates dendrite outgrowth, synaptogenesis, and neuron survival, and it was suggested that CYP46 indirectly influences beta-amyloid metabolism. CYP46 C-carriers are privileged both in terms of beta-amyloid metabolism and in terms of brain reserve due to their larger parahippocampal and hippocampal structures. The exact cellular mechanisms that translate the CYP46 allelic variation into volumetric brain differences in the parahippocampal gyrus and hippocampus are still unknown and need to be further investigated.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
06 Faculty of Arts > Institute of Psychology
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:150 Psychology
610 Medicine & health
Language:English
Date:2011
Deposited On:09 Nov 2009 15:05
Last Modified:16 Aug 2016 10:12
Publisher:Elsevier
ISSN:0197-4580
Publisher DOI:https://doi.org/10.1016/j.neurobiolaging.2009.07.001
PubMed ID:19647891
Permanent URL: https://doi.org/10.5167/uzh-23746

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