Genetic associations with brain amyloidosis: Genetics/genetic factors of Alzheimer's disease. (7th December 2020)

• Record Type: Journal Article
• Authors: Raghavan, Neha S.; Dumitrescu, Logan; Mormino, Elizabeth C.; Mahoney, Emily R.; Lee, Annie; Gao, Yizhe; Bilgel, Murat; Goldstein, David B.; Harrison, Theresa M.; Engelman, Corinne D.; Saykin, Andrew J.; Whelan, Christopher; Liu, Jimmy; Jagust, William J.; Albert, Marilyn S.; Johnson, Sterling C.; Yang, Hyun‐Sik; Johnson, Keith A.; Aisen, Paul S.; Resnick, Susan M.; Sperling, Reisa A.; De Jager, Philip L.; Schneider, Julie A.; Bennett, David A.; Schrag, Matthew; Vardarajan, Badri N.; Hohman, Timothy J.; Mayeux, Richard
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.042191
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Genetic studies of Alzheimer's disease (AD) have focused on the clinical or pathological diagnosis as the primary outcome, but little is known about the genetic basis of the preclinical phase of the disease. Our goal was to identify the underlying genetic bases for brain amyloidosis during the preclinical phase of AD. Method: We performed genome‐wide association studies of positron emission tomography (PET) amyloid levels and meta‐analyzed the results. Genetic and imaging data were acquired from ten cohorts of primarily non‐demented individuals. The largest cohort, the A4 study (n = 3, 154) was a secondary prevention trial designed to slow cognitive decline associated with brain amyloidosis. The other, smaller longitudinal cohort studies, similar in design, provided additional amyloid PET data with existing genetic data (n = 1, 160 analyzed and n = 550 currently being analyzed). Result: We identified a locus for amyloidosis within RBFOX1 in addition to APOE along with several loci nearing significance. Conclusion: Multiple genetic loci may be associated with brain amyloidosis. Further research into these specific loci and genes will help in our understanding of the molecular bases of amyloid buildup in the brain.