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Biomarker clustering in autosomal dominant Alzheimer's disease.

Alzheimers Dement. 2022 Apr 1. doi: 10.1002/alz.12661. Epub ahead of print. PMID: 35362200.

Authors/Editors: Luckett PH, Chen C, Gordon BA, Wisch J, Berman SB, Chhatwal JP, Cruchaga C, Fagan AM, Farlow MR, Fox NC, Jucker M, Levin J, Masters CL, Mori H, Noble JM, Salloway S, Schofield PR, Brickman AM, Brooks WS, Cash DM, Fulham MJ, Ghetti B, Jack CR Jr, Vöglein J, Klunk WE, Koeppe R, Su Y, Weiner M, Wang Q, Marcus D, Koudelis D, Joseph-Mathurin N, Cash L, Hornbeck R, Xiong C, Perrin RJ, Karch CM, Hassenstab J, McDade E, Morris JC, Benzinger TLS, Bateman RJ, Ances BM; Dominantly Inherited Alzheimer Network (DIAN).
Publication Date: 2022



As the number of biomarkers used to study Alzheimer's disease (AD) continues to increase, it is important to understand the utility of any given biomarker, as well as what additional information a biomarker provides when compared to others.


We used hierarchical clustering to group 19 cross-sectional biomarkers in autosomal dominant AD. Feature selection identified biomarkers that were the strongest predictors of mutation status and estimated years from symptom onset (EYO). Biomarkers identified included clinical assessments, neuroimaging, cerebrospinal fluid amyloid, and tau, and emerging biomarkers of neuronal integrity and inflammation.


Three primary clusters were identified: neurodegeneration, amyloid/tau, and emerging biomarkers. Feature selection identified amyloid and tau measures as the primary predictors of mutation status and EYO. Emerging biomarkers of neuronal integrity and inflammation were relatively weak predictors.


These results provide novel insight into our understanding of the relationships among biomarkers and the staging of biomarkers based on disease progression.


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