Abstract
Alzheimer’s disease and related dementia (ADRD) represents a growing public health burden, especially in low- and middle-income countries. Yet, most studies focus on Non-Hispanic white (NHW) populations from high-income countries. This study investigates plasma proteomic signatures associated with amyloid pathology in African populations. Nigerian older adults from the VALIANT study and participants from a Tanzanian study, with available biomarker quantification in plasma are employed. For proteomic comparison, participants from the Canadian TRIAD cohort are included, capturing a distinct population. Here, we show that multiple proteins are differentially abundant in the plasma of p-tau217-positive individuals and in the different cognitive groups, with findings largely consistent amongst African cohorts. Comorbidities are significantly associated with protein levels and differences in plasma biomarkers levels are found between sexes. Lastly, VALIANT and TRIAD show both shared and unique protein profiles in relation to amyloid-pathology. These findings support the utility of fluid biomarkers in ADRD in African populations.
Authors and Affiliations
Ilaria Pola¹˒³⁹, Tolulope Akinyemi²˒³˒³⁹, Kubra Tan¹, Oladotun Olalusi⁴˒⁵, Wiebke Traichel¹, Giulia Giacomucci⁶, Joseph Yaria⁵, Nesrine Rahmouni⁷˒⁸, Gabriel Ogunde⁴, Olabode Oguntiloye⁵, Arthur C. Macedo⁷˒⁸, Ayotomiwa Fagbemi⁵, Eniola Cadmus⁹, Joseph Therriault⁷˒⁸, Femi Popoola⁹, Stella-Maria Paddick¹⁰˒¹¹˒¹², Catherine Dotchin¹³˒¹⁴˒¹⁵˒¹⁶˒¹⁷, Alyoce Kisoli¹⁸, Richard Walker¹⁹, Mayowa Ogunronbi⁴, Dorcas Olujobi⁴, Olaoluwa Famuyiwa⁴, Joshua Akinyemi⁴˒²⁰, Mayowa Owolabi⁴˒⁵˒²¹, Chinedu T. Udeh–Momoh²²˒²³˒²⁴, Olusola Ladokun²⁵, Margaret Pericak-Vance²⁵, Anthony Griswold²⁵, Roman Romero-Ortuno²³˒²⁶, Adesola Ogunniyi⁴˒⁵, Stephanie Debette²⁷˒²⁸˒²⁹, Brian Lawlor²³˒³⁰, Nicholas J. Ashton¹˒³¹˒³², Rajesh Kalaria⁴˒¹⁰, Henrik Zetterberg¹˒³³˒³⁴˒³⁵˒³⁶˒³⁷, Pedro Rosa-Neto⁷˒⁸˒³⁸, Rufus O. Akinyemi⁴˒⁵˒¹⁰˒²¹˒⁴⁰, and Andrea L. Benedet¹˒⁴⁰
¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
² Department of Biological Sciences, Faculty of Natural and Applied Science, Lead City University, Ibadan, Nigeria
³ Department of Biomedical Laboratory Science, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria
⁴ Neuroscience and Ageing Research Unit, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria
⁵ Department of Neurology, University College Hospital, Ibadan, Oyo, Nigeria
⁶ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
⁷ McGill Centre for Studies in Aging, Douglas Hospital Research Centre (CIUSSS de l’Ouest-de-l’Île-de-Montréal), Verdun, Quebec, MC, Canada
⁸ Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, MC, Canada
⁹ Department of Community Medicine, Faculty of Public Health, College of Medicine, University of Ibadan, Ibadan, Nigeria
¹⁰ Translational and Clinical Research Institute, Biomedical Research Centre, Newcastle University, Campus for Ageing & Vitality, Newcastle upon Tyne, UK
¹¹ Gateshead Health NHS Foundation Trust, Gateshead, UK
¹² Millennium Institute for Care Research (MiCARES), University Andres Bello, Santiago, Chile
¹³ AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
¹⁴ NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, UK
¹⁵ Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
¹⁶ Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK
¹⁷ Northumbria Healthcare NHS Foundation Trust, North Shields, Tyne and Wear, Newcastle upon Tyne, UK
¹⁸ Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical College, Moshi, Tanzania
¹⁹ Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
²⁰ Department of Epidemiology and Medical Statistics, College of Medicine, University of Ibadan, Ibadan, Nigeria
²¹ Centre for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria
²² Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA
²³ Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland
²⁴ Brain and Mind Institute, Aga Khan University, Nairobi, Kenya
²⁵ John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA
²⁶ Discipline of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin, Ireland
²⁷ Bordeaux Population Health Center, INSERM UMR U1219, University of Bordeaux, Bordeaux, France
²⁸ Department of Neurology, Institute for Neurodegenerative Diseases, CHU de Bordeaux, Bordeaux, France
²⁹ Institut du Cerveau (ICM), Paris Brain Institute, INSERM U1127, CNRS UMR 7225, Sorbonne Université, AP-HP, Paris, France
³⁰ Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland
³¹ Banner Alzheimer’s Institute, Phoenix, AZ, USA
³² Banner Sun Health Research Institute, Sun City, AZ, USA
³³ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
³⁴ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK
³⁵ UK Dementia Research Institute at UCL, London, UK
³⁶ Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
³⁷ Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
³⁸ Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA
³⁹ These authors contributed equally: Ilaria Pola, Tolulope Akinyemi
⁴⁰ These authors jointly supervised this work: Rufus O. Akinyemi, Andrea L. Benedet