A blood‐based multi‐pathway biomarker assay for early detection and staging of Alzheimer's disease across ethnic groups

Author:

Jiang Yuanbing1,Uhm Hyebin1,Ip Fanny C.23,Ouyang Li2,Lo Ronnie M. N.12,Cheng Elaine Y. L.12,Cao Xiaoyun2,Tan Clara M. C.2,Law Brian C. H.2,Ortiz‐Romero Paula45,Puig‐Pijoan Albert5678,Fernández‐Lebrero Aida45689,Contador José456,Mok Kin Y.1210,Hardy John21011,Kwok Timothy C. Y.12,Mok Vincent C. T.13,Suárez‐Calvet Marc45614,Zetterberg Henrik210111516,Fu Amy K. Y.123,Ip Nancy Y.123ORCID

Affiliation:

1. Division of Life Science State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon HKSAR China

2. Hong Kong Center for Neurodegenerative Diseases, InnoHK HKSAR China

3. Guangdong Provincial Key Laboratory of Brain Science Disease and Drug Development HKUST Shenzhen Research Institute Shenzhen Guangdong China

4. Barcelonaβeta Brain Research Center (BBRC) Pasqual Maragall Foundation Barcelona Spain

5. Hospital del Mar Research Institute Barcelona Spain

6. Cognitive Decline Unit, Department of Neurology Hospital Del Mar Barcelona Spain

7. Medicine Department Universitat Autònoma de Barcelona Barcelona Spain

8. ERA‐Net on Cardiovascular Diseases (ERA‐CVD) Consortium Barcelona Spain

9. Department of Medicine and Life Sciences Universitat Pompeu Fabra Barcelona Spain

10. Department of Neurodegenerative Disease Queen Square Institute of Neurology University College London London UK

11. UK Dementia Research Institute University College London London UK

12. Therese Pei Fong Chow Research Centre for Prevention of Dementia Division of Geriatrics Department of Medicine and Therapeutics The Chinese University of Hong Kong, Shatin HKSAR China

13. Lau Tat‐chuen Research Centre of Brain Degenerative Diseases in Chinese Gerald Choa Neuroscience Institute Lui Che Woo Institute of Innovative Medicine Li Ka Shing Institute of Health Sciences Division of Neurology Department of Medicine and Therapeutics The Chinese University of Hong Kong, Shatin HKSAR China

14. Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES) Madrid Spain

15. Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden

16. Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden

Abstract

AbstractINTRODUCTIONExisting blood‐based biomarkers for Alzheimer's disease (AD) mainly focus on its pathological features. However, studies on blood‐based biomarkers associated with other biological processes for a comprehensive evaluation of AD status are limited.METHODSWe developed a blood‐based, multiplex biomarker assay for AD that measures the levels of 21 proteins involved in multiple biological pathways. We evaluated the assay's performance for classifying AD and indicating AD‐related endophenotypes in three independent cohorts from Chinese or European‐descent populations.RESULTSThe 21‐protein assay accurately classified AD (area under the receiver operating characteristic curve [AUC] = 0.9407 to 0.9867) and mild cognitive impairment (MCI; AUC = 0.8434 to 0.8945) while also indicating brain amyloid pathology. Moreover, the assay simultaneously evaluated the changes of five biological processes in individuals and revealed the ethnic‐specific dysregulations of biological processes upon AD progression.DISCUSSIONThis study demonstrated the utility of a blood‐based, multi‐pathway biomarker assay for early screening and staging of AD, providing insights for patient stratification and precision medicine.HIGHLIGHTS The authors developed a blood‐based biomarker assay for Alzheimer's disease. The 21‐protein assay classifies AD/MCI and indicates brain amyloid pathology. The 21‐protein assay can simultaneously assess activities of five biological processes. Ethnic‐specific dysregulations of biological processes in AD were revealed.

Funder

National Key Research and Development Program of China

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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