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 Olalusi 4,5,
Wiebke Traichel1, Giulia Giacomucci6, Joseph Yaria5, Nesrine Rahmouni7,8,
Gabriel Ogunde 4, 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,
RichardWalker 19,Mayowa Ogunronbi4, DorcasOlujobi4, Olaoluwa Famuyiwa4,
Joshua Akinyemi4,20, Mayowa Owolabi4,5,21, Chinedu T. Udeh–Momoh 22,23,24,
Olusola Ladokun 2, Anthony Griswold 25, Roman Romero-Ortuno 23,26,
Margaret Pericak-Vance 25, Adesola Ogunniyi4,5, Stephanie Debette27,28,29,
Brian Lawlor23,30, Nicholas J. Ashton1,31,32, Rajesh Kalaria 4,10,
Henrik Zetterberg 1,33,34,35,36,37, Pedro Rosa-Neto7,8,38,
Rufus O. Akinyemi4,5,10,21,40 & Andrea L. Benedet 1,40
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg,
Mölndal, Sweden. 2Department of Biological Sciences, Faculty of Natural and Applied Science, Lead City University, Ibadan, Nigeria. 3Department of
Biomedical Laboratory Science, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria. 4Neuroscience and Ageing
Research Unit, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria. 5Department of Neurology,
University College Hospital, Ibadan, Oyo, Nigeria. 6Department of Neuroscience, Psychology, Drug Research and Child Health, University of
Florence, Florence, Italy. 7McGill Centre for Studies in Aging, Douglas Hospital Research Centre (CIUSSS de l’Ouest-de-l’Île-de-Montréal), Verdun,
Quebec, MC, Canada. 8Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, MC, Canada. 9Department
of Community Medicine, Faculty of Public Health, College of Medicine, University of Ibadan, Ibadan, Nigeria. 10Translational and Clinical Research
Institute, Biomedical Research Centre, Newcastle University, Campus for Ageing & Vitality, Newcastle upon Tyne, UK. 11Gateshead Health NHS Foundation
Trust, Gateshead, UK. 12Millennium Institute for Care Research (MiCARES), University Andres Bello, Santiago, Chile. 13AGE Research Group, Translational
and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. 14NIHR Newcastle Biomedical Research
Centre, Newcastle upon Tyne, UK. 15Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. 16Cumbria, Northumberland, Tyne
and Wear NHS Foundation Trust, Newcastle upon Tyne, UK. 17Northumbria Healthcare NHS Foundation Trust, North Shields, Tyne and Wear, Newcastle
upon Tyne, UK. 18Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical College, Moshi, Tanzania. 19Population Health Sciences Institute,
Newcastle University, Newcastle upon Tyne, UK. 20Department of Epidemiology and Medical Statistics, College of Medicine, University of Ibadan,
Ibadan, Nigeria. 21Centre for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria. 22Division of Public Health
Sciences, Wake Forest University School of Medicine, Winston-, Salem, NC, USA. 23Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland.
24Brain and Mind Institute, Aga Khan University, Nairobi, Kenya. 25John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of
Miami, Miami, FL, USA. 26Discipline of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin, Ireland. 27Bordeaux Population Health
Center, INSERM UMR U1219, University of Bordeaux, Bordeaux, France. 28Department of Neurology, Institute for Neurodegenerative Diseases, CHU de
Bordeaux, Bordeaux, France. 29Institut du Cerveau (ICM), Paris Brain Institute, INSERM U1127, CNRS UMR 7225, Sorbonne Université, AP-HP, Paris, France.
30Trinity College Institute of Neuroscience, School of Psychology, Trinity College Dublin, Dublin, Ireland. 31Banner Alzheimer’s Institute, Phoenix, AZ, USA.
32Banner Sun Health Research Institute, Sun City, AZ, USA. 33Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
34Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK. 35UK Dementia Research Institute at UCL,
London, UK. 36Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
37Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 38Peter O’Donnell
Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. 39These authors contributed equally: Ilaria Pola, Tolulope Akinyemi.
40These authors jointly supervised this work: Rufus O. Akinyemi, Andrea L. Benedet.