Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936.
The APOE ε and TOMM40 rs10524523 ('523') variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer's disease (AD) related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impai...
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oai:doaj.org-article:4b656b486d5a421890436bac0f1814b12021-11-18T08:46:14ZAlzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936.1932-620310.1371/journal.pone.0080513https://doaj.org/article/4b656b486d5a421890436bac0f1814b12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24260406/?tool=EBIhttps://doaj.org/toc/1932-6203The APOE ε and TOMM40 rs10524523 ('523') variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer's disease (AD) related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 '523' genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 '523' poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636). No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1) their specific techniques in adjusting for brain size; 2) assessing more detailed sub-divisions of the hippocampal formation; and 3) testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy.Donald M LyallNatalie A RoyleSarah E HarrisMark E BastinSusana Muñoz ManiegaCatherine MurrayMichael W LutzAnn M SaundersAllen D RosesMaria C del Valdés HernándezJohn M StarrDavid J PorteousJoanna M WardlawIan J DearyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80513 (2013) |
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Medicine R Science Q |
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Medicine R Science Q Donald M Lyall Natalie A Royle Sarah E Harris Mark E Bastin Susana Muñoz Maniega Catherine Murray Michael W Lutz Ann M Saunders Allen D Roses Maria C del Valdés Hernández John M Starr David J Porteous Joanna M Wardlaw Ian J Deary Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936. |
| description |
The APOE ε and TOMM40 rs10524523 ('523') variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer's disease (AD) related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 '523' genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 '523' poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636). No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1) their specific techniques in adjusting for brain size; 2) assessing more detailed sub-divisions of the hippocampal formation; and 3) testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy. |
| format |
article |
| author |
Donald M Lyall Natalie A Royle Sarah E Harris Mark E Bastin Susana Muñoz Maniega Catherine Murray Michael W Lutz Ann M Saunders Allen D Roses Maria C del Valdés Hernández John M Starr David J Porteous Joanna M Wardlaw Ian J Deary |
| author_facet |
Donald M Lyall Natalie A Royle Sarah E Harris Mark E Bastin Susana Muñoz Maniega Catherine Murray Michael W Lutz Ann M Saunders Allen D Roses Maria C del Valdés Hernández John M Starr David J Porteous Joanna M Wardlaw Ian J Deary |
| author_sort |
Donald M Lyall |
| title |
Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936. |
| title_short |
Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936. |
| title_full |
Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936. |
| title_fullStr |
Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936. |
| title_full_unstemmed |
Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936. |
| title_sort |
alzheimer's disease susceptibility genes apoe and tomm40, and hippocampal volumes in the lothian birth cohort 1936. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/4b656b486d5a421890436bac0f1814b1 |
| work_keys_str_mv |
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