DAT1 and BDNF polymorphisms interact to predict Aβ and tau pathology

• Published in: Neurobiology of aging 2024-01, Vol.133, p.115-124
• Main Authors: Ciampa, Claire J, Morin, Thomas M, Murphy, Alice, Joie, Renaud La, Landau, Susan M, Berry, Anne S
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Amyloid beta-Peptides; Atrophy; Biomarkers; Brain-Derived Neurotrophic Factor - genetics; Cognitive Dysfunction - genetics; Cross-Sectional Studies; Humans; Positron-Emission Tomography; tau Proteins - genetics
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2023.10.009

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.