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

Yuanbing Jiang; Hyebin Uhm; Fanny C Ip; Li Ouyang; Ronnie M N Lo; Elaine Y L Cheng; Xiaoyun Cao; Clara M C Tan; Brian C H Law; Paula Ortiz-Romero; Albert Puig-Pijoan; Aida Fernández-Lebrero; José Contador; Kin Y Mok; John Hardy; Timothy C Y Kwok; Vincent C T Mok; Marc Suárez-Calvet; Henrik Zetterberg; Amy K Y Fu; Nancy Y Ip

doi:10.1002/alz.13676

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

Alzheimers Dement. 2024 Mar;20(3):2000-2015. doi: 10.1002/alz.13676. Epub 2024 Jan 6.

Authors

Yuanbing Jiang¹, Hyebin Uhm¹, Fanny C Ip^{2

3}, Li Ouyang², Ronnie M N Lo^{1

2}, Elaine Y L Cheng^{1

2}, Xiaoyun Cao², Clara M C Tan², Brian C H Law², Paula Ortiz-Romero^{4

5}, Albert Puig-Pijoan^{5

6

7

8}, Aida Fernández-Lebrero^{4

5

6

8

9}, José Contador^{4

5

6}, Kin Y Mok^{1

2

10}, John Hardy^{2

10

11}, Timothy C Y Kwok¹², Vincent C T Mok¹³, Marc Suárez-Calvet^{4

5

6

14}, Henrik Zetterberg^{2

10

11

15

16

17}, Amy K Y Fu^{1

2

3}, Nancy Y Ip^{1

2

3}

Affiliations

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.
¹⁷ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Abstract

Introduction: Existing 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.

Methods: We 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.

Results: The 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.

Discussion: This 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.

Keywords: Alzheimer's disease; amyloid pathology; blood biomarkers; disease staging; early detection; patient stratification; precision medicine.

MeSH terms

Alzheimer Disease* / diagnosis
Alzheimer Disease* / pathology
Amyloid beta-Peptides
Biomarkers
Cognitive Dysfunction* / diagnosis
Cognitive Dysfunction* / pathology
Ethnicity
Humans
tau Proteins

Substances

Biomarkers
Amyloid beta-Peptides
tau Proteins

Abstract

MeSH terms

Substances

Grants and funding