The Dementia SomaSignal Test (dSST): A plasma proteomic predictor of 20-year dementia risk

被引：0

作者：

Duggan, Michael R. ^{[1
]}

Paterson, Clare ^{[2
]}

Lu, Yifei ^{[3
]}

Biegel, Hannah ^{[2
]}

Dark, Heather E. ^{[1
]}

Cordon, Jenifer ^{[1
]}

Bilgel, Murat ^{[1
]}

Kaneko, Naoto ^{[4
]}

Shibayama, Masaki ^{[4
]}

Kato, Shintaro ^{[4
,5
]}

Furuichi, Makio ^{[4
,5
]}

Waga, Iwao ^{[4
,5
,6
]}

Hiraga, Keita ^{[7
]}

Katsuno, Masahisa ^{[7
,8
]}

Nishita, Yukiko ^{[9
]}

Otsuka, Rei ^{[9
]}

Davatzikos, Christos ^{[10
]}

Erus, Guray ^{[10
]}

Loupy, Kelsey ^{[2
]}

Simpson, Melissa ^{[2
]}

Lewis, Alexandria ^{[11
]}

Moghekar, Abhay ^{[11
]}

Palta, Priya ^{[12
]}

Gottesman, Rebecca F. ^{[13
]}

Resnick, Susan M. ^{[1
]}

Coresh, Josef ^{[14
,15
]}

Williams, Stephen A. ^{[2
]}

Walker, Keenan A. ^{[1
]}

机构：

[1] NIA, Lab Behav Neurosci, NIH, NIH BRC BG RM 04B311,251 Bayview Blvd, Baltimore, MD 21224 USA

[2] Stand BioTools, Dept Clin & Res Dev, Boulder, CO USA

[3] Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA

[4] NEC Solut Innovators Ltd, Koto Ku, Tokyo, Japan

[5] SkymatiX Inc, Chuo City, Tokyo 1030021, Japan

[6] Tohoku Univ, Wellbeing Design Inst Hlth, Aoba ku, Sendai, Japan

[7] Nagoya Univ, Grad Sch Med, Dept Neurol, Nagoya, Aichi, Japan

[8] Nagoya Univ, Grad Sch Med, Dept Clin Res Educ, Nagoya, Aichi, Japan

[9] Natl Ctr Geriatr & Gerontol, Dept Epidemiol Aging, Obu, Aichi, Japan

[10] Univ Penn, Perelman Sch Med, Artificial Intelligence Biomed Imaging Lab, Philadelphia, PA USA

[11] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA

[12] Univ North Carolina Chapel Hill, Dept Neurol, Chapel Hill, NC USA

[13] NINDS, Stroke Branch, Bethesda, MD USA

[14] New York Univ Grossman Sch Med, Dept Populat Hlth, New York, NY USA

[15] New York Univ Grossman Sch Med, Dept Med, New York, NY USA

来源：

ALZHEIMERS & DEMENTIA | 2025年 / 21卷 / 02期

基金：

美国国家卫生研究院;

关键词：

dementia; machine learning; prognosis; proteomics; ALZHEIMERS-DISEASE; OLDER-ADULTS; PATTERNS; AD; CLASSIFICATION; REGULARIZATION; PROGRESSION; ATROPHY; SCORE;

D O I：

10.1002/alz.14549

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

INTRODUCTIONThere is an unmet need for tools to quantify dementia risk during its multi-decade preclinical/prodromal phase, given that current biomarkers predict risk over shorter follow-up periods and are specific to Alzheimer's disease.METHODSUsing high-throughput proteomic assays and machine learning techniques in the Atherosclerosis Risk in Communities study (n = 11,277), we developed the Dementia SomaSignal Test (dSST).RESULTSIn addition to outperforming existing plasma biomarkers, the dSST predicted mid-life dementia risk over a 20-year follow-up across two independent cohorts with different ethnic backgrounds (areas under the curve [AUCs]: dSST 0.68-0.70, dSST+age 0.75-0.81). In a separate cohort, the dSST was associated with longitudinal declines across multiple cognitive domains, accelerated brain atrophy, and elevated measures of neuropathology (as evidenced by positron emission tomography and plasma biomarkers).DISCUSSIONThe dSST is a cost-effective, scalable, and minimally invasive protein-based prognostic aid that can quantify risk up to two decades before dementia onset.Highlights The Dementia SomaSignal Test (dSST) predicts 20-year dementia risk across two independent cohorts. dSST outperforms existing plasma biomarkers in predicting multi-decade dementia risk. dSST predicts cognitive decline and accelerated brain atrophy in a third cohort. dSST is a prognostic aid that can predict dementia risk over two decades.

引用

页数：18

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