DAT1 和 BDNF 多态性相互作用预测 Aβ 和 tau 病理学。
DAT1 and BDNF polymorphisms interact to predict Aβ and tau pathology.
机构信息
Department of Biology, Brandeis University, Waltham, MA 02453, USA.
Department of Psychology, Brandeis University, Waltham, MA 02453, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA 02155, USA.
出版信息
Neurobiol Aging. 2024 Jan;133:115-124. doi: 10.1016/j.neurobiolaging.2023.10.009. Epub 2023 Oct 31.
Previous work has associated polymorphisms in the dopamine transporter gene (rs6347 in DAT1/SLC6A3) and brain derived neurotrophic factor gene (Val66Met in BDNF) with atrophy and memory decline. However, it is unclear whether these polymorphisms relate to atrophy and cognition through associations with Alzheimer's disease pathology. We tested for effects of DAT1 and BDNF polymorphisms on cross-sectional and longitudinal β-amyloid (Aβ) and tau pathology (measured with positron emission tomography (PET)), hippocampal volume, and cognition. We analyzed a sample of cognitively normal older adults (cross-sectional n = 321) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). DAT1 and BDNF interacted to predict Aβ-PET, tau-PET, and hippocampal atrophy. Carriers of both "non-boptimal" DAT1 C and BDNF Met alleles demonstrated greater pathology and atrophy. Our findings provide novel links between dopamine and neurotrophic factor genes and AD pathology, consistent with previous research implicating these variants in greater risk for developing AD.
先前的研究将多巴胺转运体基因（DAT1/SLC6A3 中的 rs6347）和脑源性神经营养因子基因（BDNF 中的 Val66Met）的多态性与萎缩和记忆衰退联系起来。然而，目前尚不清楚这些多态性是否通过与阿尔茨海默病病理学的关联与萎缩和认知相关。我们测试了 DAT1 和 BDNF 多态性对横断面和纵向β-淀粉样蛋白（Aβ）和 tau 病理学（通过正电子发射断层扫描（PET）测量）、海马体积和认知的影响。我们分析了来自阿尔茨海默病神经影像学倡议（ADNI）的认知正常的老年成年人（横断面 n=321）样本。DAT1 和 BDNF 相互作用可预测 Aβ-PET、tau-PET 和海马萎缩。同时携带“非最佳”DAT1 C 和 BDNF Met 等位基因的个体表现出更大的病理学和萎缩。我们的发现为多巴胺和神经营养因子基因与 AD 病理学之间提供了新的联系，这与先前的研究表明这些变体与 AD 发病风险增加有关。
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