4.6 Article

The impact of Alzheimer's disease susceptibility loci on lateral ventricular surface morphology in older adults

Journal

BRAIN STRUCTURE & FUNCTION
Volume 227, Issue 3, Pages 913-924

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00429-021-02429-y

Keywords

Lateral ventricle; Genetic; Morphology; Alzheimer's disease; sMRI

Funding

  1. Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
  2. DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
  3. National Institute on Aging
  4. National Institute of Biomedical Imaging and Bioengineering
  5. AbbVie
  6. Alzheimer's Association
  7. Alzheimer's Drug Discovery Foundation
  8. Araclon Biotech
  9. BioClinica, Inc.
  10. Biogen
  11. Bristol-Myers Squibb Company
  12. CereSpir, Inc.
  13. Cogstate
  14. Eisai Inc.
  15. Elan Pharmaceuticals, Inc.
  16. Eli Lilly and Company
  17. EuroImmun
  18. F. Hoffmann-La Roche Ltd
  19. Genentech, Inc.
  20. Fujirebio
  21. GE Healthcare
  22. IXICO Ltd.
  23. Janssen Alzheimer Immunotherapy Research & Development, LLC.
  24. Johnson & Johnson Pharmaceutical Research & Development LLC.
  25. Lumosity
  26. Lundbeck
  27. Merck Co., Inc.
  28. Meso Scale Diagnostics, LLC.
  29. NeuroRx Research
  30. Neurotrack Technologies
  31. Novartis Pharmaceuticals Corporation
  32. Pfizer Inc.
  33. Piramal Imaging
  34. Servier
  35. Takeda Pharmaceutical Company
  36. Transition Therapeutics
  37. The Canadian Institutes of Health Research

Ask authors/readers for more resources

The enlargement of ventricular volume is a common trend in the elderly, especially in AD patients. A study investigated the impact of AD susceptibility loci on the surface features of the lateral ventricle and found that variations in these loci significantly accelerated the atrophy of the lateral ventricle. The study also revealed negative correlations between cognitive scores and various regions of the ventricular surface, supporting the importance of the lateral ventricle in cognition in the elderly.
The enlargement of ventricular volume is a general trend in the elderly, especially in patients with Alzheimer's disease (AD). Multiple susceptibility loci have been reported to have an increased risk for AD and the morphology of brain structures are affected by the variations in the risk loci. Therefore, we hypothesized that genes contributed significantly to the ventricular surface, and the changes of ventricular surface were associated with the impairment of cognitive functions. After the quality controls (QC) and genotyping, a lateral ventricular segmentation method was employed to obtain the surface features of lateral ventricle. We evaluated the influence of 18 selected AD susceptibility loci on both volume and surface morphology across 410 subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI). Correlations were conducted between radial distance (RD) and Montreal Cognitive Assessment (MoCA) subscales. Only the C allele at the rs744373 loci in BIN1 gene significantly accelerated the atrophy of lateral ventricle, including the anterior horn, body, and temporal horn of left lateral ventricle. No significant effect on lateral ventricle was found at other loci. Our results revealed that most regions of the bilateral ventricular surface were significantly negatively correlated with cognitive scores, particularly in delayed recall. Besides, small areas of surface were negatively correlated with language, orientation, and visuospatial scores. Together, our results indicated that the genetic variation affected the localized areas of lateral ventricular surface, and supported that lateral ventricle was an important brain structure associated with cognition in the elderly.

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