DAT1 and BDNF polymorphisms interact to predict Aβ and tau pathology

Claire J Ciampa; Thomas M Morin; Alice Murphy; Renaud La Joie; Susan M Landau; Anne S Berry; Alzheimer’s Disease Neuroimaging Initiative

doi:10.1016/j.neurobiolaging.2023.10.009

DAT1 and BDNF polymorphisms interact to predict Aβ and tau pathology

Neurobiol Aging. 2024 Jan:133:115-124. doi: 10.1016/j.neurobiolaging.2023.10.009. Epub 2023 Oct 31.

Authors

Claire J Ciampa¹, Thomas M Morin², Alice Murphy³, Renaud La Joie⁴, Susan M Landau⁵, Anne S Berry⁶; Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ Department of Biology, Brandeis University, Waltham, MA 02453, USA. Electronic address: claireciampa@brandeis.edu.
² Department of Psychology, Brandeis University, Waltham, MA 02453, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA 02155, USA.
³ Hellen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
⁴ Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USA.
⁵ Hellen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
⁶ Department of Psychology, Brandeis University, Waltham, MA 02453, USA; Volen Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA.

PMID: 37948982
PMCID: PMC10872994 (available on 2025-01-01)
DOI: 10.1016/j.neurobiolaging.2023.10.009

Abstract

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.

Keywords: ADNI; Amyloid PET; Brain derived neurotrophic factor gene; Dopamine transporter gene; Hippocampal atrophy; Tau PET.

MeSH terms

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

Substances

Brain-Derived Neurotrophic Factor
Amyloid beta-Peptides
tau Proteins
Biomarkers

Abstract

MeSH terms

Substances

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