Biomarker clustering in autosomal dominant Alzheimer's disease

被引：6

作者：

Luckett, Patrick H. ^{[1
]}

Chen, Charlie ^{[1
]}

Gordon, Brian A. ^{[1
]}

Wisch, Julie ^{[1
]}

Berman, Sarah B. ^{[2
]}

Chhatwal, Jasmeer P. ^{[3
]}

Cruchaga, Carlos ^{[1
]}

Fagan, Anne M. ^{[1
]}

Farlow, Martin R. ^{[4
]}

Fox, Nick C. ^{[5
]}

Jucker, Mathias ^{[6
,7
]}

Levin, Johannes ^{[8
,9
,10
]}

Masters, Colin L. ^{[11
]}

Mori, Hiroshi ^{[12
]}

Noble, James M. ^{[13
,14
]}

Salloway, Stephen ^{[15
,16
]}

Schofield, Peter R. ^{[17
,18
]}

Brickman, Adam M. ^{[19
,20
]}

Brooks, William S. ^{[17
,18
]}

Cash, David M. ^{[5
]}

Fulham, Michael J. ^{[19
,20
]}

Ghetti, Bernardino ^{[4
]}

Jack, Clifford R., Jr. ^{[21
]}

Voeglein, Jonathan ^{[22
,23
]}

Klunk, William E. ^{[2
]}

Koeppe, Robert ^{[24
]}

Su, Yi ^{[25
]}

Weiner, Michael ^{[26
,27
]}

Wang, Qing ^{[1
]}

Marcus, Daniel ^{[1
]}

Koudelis, Deborah ^{[1
]}

Joseph-Mathurin, Nelly ^{[1
]}

Cash, Lisa ^{[1
]}

Hornbeck, Russ ^{[1
]}

Xiong, Chengjie ^{[1
]}

Perrin, Richard J. ^{[1
]}

Karch, Celeste M. ^{[1
]}

Hassenstab, Jason ^{[1
]}

McDade, Eric ^{[1
]}

Morris, John C. ^{[1
]}

Benzinger, Tammie L. S. ^{[1
]}

Bateman, Randall J. ^{[1
]}

Ances, Beau M. ^{[1
]}

机构：

[1] Washington Univ St Louis, St Louis, MO USA

[2] Univ Pittsburgh, Pittsburgh, PA USA

[3] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA

[4] Indiana Univ, Bloomington, IN USA

[5] UCL Queen Sq Inst Neurol, Dementia Res Ctr, London, England

[6] German Ctr Neurodegenerat Dis, Tubingen, Germany

[7] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany

[8] Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany

[9] German Ctr Neurodegenerat Dis, Munich, Germany

[10] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[11] Univ Melbourne, Florey Inst, Parkville, Vic, Australia

[12] Nagaoka Sutoku Univ, Osaka City Univ, Sch Med, Abeno Ku, Osaka, Japan

[13] Columbia Univ Irving Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, GH Sergievsky Ctr, New York, NY USA

[14] Columbia Univ Irving Med Ctr, Dept Neurol, New York, NY USA

[15] Brown Univ, Butler Hosp, Providence, RI 02912 USA

[16] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA

[17] Neurosci Res Australia, Randwick, NSW, Australia

[18] Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia

[19] Royal Prince Alfred Hosp, Dept Mol Imaging, Camperdown, NSW, Australia

[20] Univ Sydney, Sydney, NSW, Australia

[21] Mayo Clin, Rochester, MN USA

[22] Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany

[23] German Ctr Neurodegenerat Dis DZNE, Munich, Germany

[24] Univ Michigan, Ann Arbor, MI 48109 USA

[25] Banner Alzheimer Inst, Phoenix, AZ USA

[26] Univ Calif San Francisco, San Francisco, CA 94143 USA

[27] San Francisco VA Med Ctr, San Francisco, CA USA

来源：

ALZHEIMERS & DEMENTIA | 2023年 / 19卷 / 01期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

Autosomal dominant Alzheimer's disease; biomarkers; machine learning; FLUID BIOMARKER; PET; YKL-40;

D O I：

10.1002/alz.12661

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：274 / 284

页数：11

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