Biomarker clustering in autosomal dominant Alzheimer's disease.

Abstract

INTRODUCTION:

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.

METHODS:

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.

RESULTS:

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.

DISCUSSION:

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

• Authors: Patrick H Luckett, Charlie Chen, Brian A Gordon, Julie Wisch, Sarah B Berman, Jasmeer P Chhatwal, Carlos Cruchaga, Anne M Fagan, Martin R Farlow, Nick C Fox, Mathias Jucker, Johannes Levin, Colin L Masters, Hiroshi Mori, James M Noble, Stephen Salloway, Peter R Schofield, Adam M Brickman, William S Brooks, David M Cash, Michael J Fulham, Bernardino Ghetti, Clifford R Jack Jr, Jonathan Vöglein, William E Klunk, Robert Koeppe, Yi Su, Michael Weiner, Qing Wang, Daniel Marcus, Deborah Koudelis, Nelly Joseph-Mathurin, Lisa Cash, Russ Hornbeck, Chengjie Xiong, Richard J Perrin, Celeste M Karch, Jason Hassenstab, Eric McDade, John C Morris, Tammie L S Benzinger, Randall J Bateman, Beau M Ances, Dominantly Inherited Alzheimer Network (DIAN)
• Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association (Alzheimers Dement) Vol. 19 Issue 1 Pg. 274-284 (01 2023) ISSN: 1552-5279 [Electronic] United States
• PMID: 35362200 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2022 the Alzheimer's Association.

Chemical References

• Amyloid beta-Peptides
• Amyloidogenic Proteins
• Biomarkers
• tau Proteins

Topics

• Humans
• Alzheimer Disease (diagnosis)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Amyloidogenic Proteins
• Biomarkers (cerebrospinal fluid)
• Cross-Sectional Studies
• Inflammation
• tau Proteins (genetics, cerebrospinal fluid)