Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative

Erlan Sanchez; Tim Wilkinson; Gillian Coughlan; Saira Mirza; Andrée-Ann Baril; Joel Ramirez; Malcolm A Binns; Sandra E Black; Michael Borrie; Allison A Dilliott; Roger A Dixon; Dar Dowlatshahi; Sali Farhan; Elizabeth Finger; Corinne E Fischer; Andrew Frank; Morris Freedman; Rafaella A Goncalves; David A Grimes; Ayman Hassan; Robert A Hegele; Sanjeev Kumar; Anthony E Lang; Connie Marras; Paula M McLaughlin; Joseph B Orange; Stephen H Pasternak; Bruce G Pollock; Tarek K Rajji; Angela C Roberts; John F Robinson; Ekaterina Rogaeva; Demetrios J Sahlas; Gustavo Saposnik; Michael J Strong; Richard H Swartz; David F Tang-Wai; Maria Carmela Tartaglia; Angela K Troyer; Hlin Kvartsberg; Henrik Zetterberg; Douglas P Munoz; ONDRI Investigators; Mario Masellis

doi:10.1002/alz.13560

Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative

Alzheimers Dement. 2024 Mar;20(3):1753-1770. doi: 10.1002/alz.13560. Epub 2023 Dec 17.

Authors

Erlan Sanchez¹, Tim Wilkinson¹, Gillian Coughlan², Saira Mirza^{1

3}, Andrée-Ann Baril⁴, Joel Ramirez⁵, Malcolm A Binns^{6

7}, Sandra E Black^{3

5}, Michael Borrie^{8

9}, Allison A Dilliott¹⁰, Roger A Dixon¹¹, Dar Dowlatshahi^{12

13}, Sali Farhan¹⁰, Elizabeth Finger^{8

9}, Corinne E Fischer¹⁴, Andrew Frank¹⁵, Morris Freedman^{3

6

16}, Rafaella A Goncalves¹⁷, David A Grimes^{12

13

18}, Ayman Hassan¹⁹, Robert A Hegele^{9

20}, Sanjeev Kumar^{21

22}, Anthony E Lang^{3

23}, Connie Marras²³, Paula M McLaughlin^{24

25}, Joseph B Orange^{26

27}, Stephen H Pasternak^{28

29}, Bruce G Pollock^{21

22

30}, Tarek K Rajji^{21

22}, Angela C Roberts^{26

27}, John F Robinson^{9

20}, Ekaterina Rogaeva³¹, Demetrios J Sahlas³², Gustavo Saposnik^{3

33}, Michael J Strong^{9

34}, Richard H Swartz^{3

35}, David F Tang-Wai^{3

36}, Maria Carmela Tartaglia^{31

36}, Angela K Troyer^{37

38}, Hlin Kvartsberg^{39

40}, Henrik Zetterberg^{39

40

41

42

43}, Douglas P Munoz¹⁷; ONDRI Investigators; Mario Masellis^{1

3}

Affiliations

¹ L.C. Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
² Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁴ Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
⁵ Dr. Sandra Black Centre for Brain Resilience & Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
⁶ Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
⁷ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁸ Lawson Health Research Institute, London, Ontario, Canada.
⁹ Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
¹⁰ Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada.
¹¹ Department of Psychology, Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
¹² Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
¹³ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
¹⁴ Keenan Research Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
¹⁵ Bruyere Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
¹⁶ Department of Medicine, Mt. Sinai Hospital, Toronto, Ontario, Canada.
¹⁷ Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
¹⁸ Brain and Mind Research Institute, Ottawa, Ontario, Canada.
¹⁹ Thunder Bay Regional Research Institute, Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada.
²⁰ Robarts Research Institute, Western University, London, Ontario, Canada.
²¹ Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
²² Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
²³ Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, Toronto, Ontario, Canada.
²⁴ Nova Scotia Health, Halifax, Nova Scotia, Canada.
²⁵ Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
²⁶ School of Communication Sciences and Disorders, Western University, London, Ontario, Canada.
²⁷ Canadian Centre for Activity and Aging, Western University, London, Ontario, Canada.
²⁸ Department of Clinical Neurological Sciences, Robarts Research Institute, Western University, London, Ontario, Canada.
²⁹ Parkwood Institute, St. Joseph's Health Care Centre, Western University, London, Ontario, Canada.
³⁰ Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
³¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
³² McMaster University, Hamilton, Ontario, Canada.
³³ Stroke Outcomes and Decision Neuroscience Unit, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
³⁴ Canadian Institutes for Health Research, Ottawa, Ontario, Canada.
³⁵ Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
³⁶ Krembil Brain Institute Memory Clinic, University Health Network, Toronto, Ontario, Canada.
³⁷ Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
³⁸ Neuropsychology and Cognitive Health, Baycrest Health Sciences, Toronto, Ontario, Canada.
³⁹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁴¹ Dementia Research Institute, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
⁴² Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
⁴³ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin, Madison, Wisconsin, USA.

Abstract

Introduction: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases.

Methods: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aβ)_42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD).

Results: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aβ_42/40 .

Discussion: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.

Keywords: activities of daily living; amyloid; amyloid beta; blood; blood-based; cognition; dementia; glial fibrillary acidic protein; longitudinal; neurofilament light chain; neuropsychiatric; phosphorylated tau; protein; tau; vascular.

MeSH terms

Activities of Daily Living
Alzheimer Disease*
Amyloid beta-Peptides
Biomarkers
Cardiovascular Diseases*
Cognition
Cognitive Dysfunction*
Frontotemporal Dementia*
Humans
Neurodegenerative Diseases*
Ontario
tau Proteins

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins

Abstract

MeSH terms

Substances

Grants and funding