دورية أكاديمية
Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE-ε4/TOMM40 long poly-T repeat allele variants.
| العنوان: | Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE-ε4/TOMM40 long poly-T repeat allele variants. |
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| المؤلفون: | Prokopenko, I, Miyakawa, G, Zheng, B, Heikkinen, J, Petrova Quayle, D, Udeh-Momoh, C, Claringbould, A, Neumann, J, Haytural, H, Kaakinen, MA, Loizidou, E, Meissner, E, Bertram, L, BIOS consortium, Gveric, DO, Gentleman, SM, Attems, J, Perneczky, R, Arzberger, T, Muglia, P, Lill, CM, Parkkinen, L, Middleton, LT |
| المصدر: | 824 ; 814 |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2019 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | APOE, Alzheimer's disease, Apolipoprotein E, Association analysis, Brain banks, Dementia with Lewy bodies, Lewy body dementias, Neuropathology, Parkinson's disease, Parkinson's disease dementia, TOMM40, BIOS consortium |
| جغرافية الموضوع: | United States |
| الوصف: | Introduction: The role of TOMM40-APOE 19q13.3 region variants is well documented in Alzheimer's disease (AD) but remains contentious in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Methods: We dissected genetic profiles within the TOMM40-APOE region in 451 individuals from four European brain banks, including DLB and PDD cases with/without neuropathological evidence of AD-related pathology and healthy controls. Results: TOMM40-L/APOE-ε4 alleles were associated with DLB (OR TOMM40 -L = 3.61; P value = 3.23 × 10-9; OR APOE -ε4 = 3.75; P value = 4.90 × 10-10) and earlier age at onset of DLB (HR TOMM40 -L = 1.33, P value = .031; HR APOE -ε4 = 1.46, P value = .004), but not with PDD. The TOMM40-L/APOE-ε4 effect was most pronounced in DLB individuals with concomitant AD pathology (OR TOMM40 -L = 4.40, P value = 1.15 × 10-6; OR APOE -ε4 = 5.65, P value = 2.97 × 10-8) but was not significant in DLB without AD. Meta-analyses combining all APOE-ε4 data in DLB confirmed our findings (ORDLB = 2.93, P value = 3.78 × 10-99; ORDLB+AD = 5.36, P value = 1.56 × 10-47). Discussion: APOE-ε4/TOMM40-L alleles increase susceptibility and risk of earlier DLB onset, an effect explained by concomitant AD-related pathology. These findings have important implications in future drug discovery and development efforts in DLB. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1552-5260 |
| العلاقة: | Alzheimers & Dementia; http://hdl.handle.net/10044/1/76129Test |
| DOI: | 10.1016/j.trci.2019.08.005 |
| الإتاحة: | https://doi.org/10.1016/j.trci.2019.08.005Test http://hdl.handle.net/10044/1/76129Test |
| حقوق: | © 2019 The Authors. This is an open access article under the CC BY‐NC‐ND license (http://creativecommons.org/licenses/byTest‐nc‐nd/4.0/). |
| رقم الانضمام: | edsbas.C4F375AB |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15525260 |
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| DOI: | 10.1016/j.trci.2019.08.005 |