کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5622771 1579254 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Featured ArticleGenetic epistasis regulates amyloid deposition in resilient aging
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Featured ArticleGenetic epistasis regulates amyloid deposition in resilient aging
چکیده انگلیسی


- Brain-derived neurotrophic factor (BDNF) Val66Met interacts with SORL1 variants to impact expression of SORL1-005.
- SORL1-005 may influence diffuse rather than neuritic amyloid pathology in postmortem brain.
- The BDNF-SORL1 interaction effect is present in individuals without confirmed Alzheimer's disease.
- In vivo amyloid, measured by positron emission tomography imaging, is also impacted by the BDNF-SORL1 interaction.

IntroductionThe brain-derived neurotrophic factor (BDNF) interacts with important genetic Alzheimer's disease (AD) risk factors. Specifically, variants within the SORL1 gene determine BDNF's ability to reduce amyloid β (Aβ) in vitro. We sought to test whether functional BDNF variation interacts with SORL1 genotypes to influence expression and downstream AD-related processes in humans.MethodsWe analyzed postmortem brain RNA sequencing and neuropathological data for 441 subjects from the Religious Orders Study/Memory and Aging Project and molecular and structural neuroimaging data for 1285 subjects from the Alzheimer's Disease Neuroimaging Initiative.ResultsWe found one SORL1 RNA transcript strongly regulated by SORL1-BDNF interactions in elderly without pathological AD and showing stronger associations with diffuse than neuritic Aβ plaques. The same SORL1-BDNF interactions also significantly influenced Aβ load as measured with [18F]Florbetapir positron emission tomography.DiscussionOur results bridge the gap between risk and resilience factors for AD, demonstrating interdependent roles of established SORL1 and BDNF functional genotypes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Alzheimer's & Dementia - Volume 13, Issue 10, October 2017, Pages 1107-1116
نویسندگان
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