Guidelines for the standardization of pre-analytical variables for salivary biomarker studies in Alzheimer's disease research: An updated review and consensus of the Salivary Biomarkers for Dementia Research Working Group.
Henrik Zetterberg, Paul D Slowey, Gustavo Alves Andrade Dos Santos, Eva Carro, Sid O' Bryant, Charisse N Winston, Helena Sophia Gleerup, Mei-Ann Lim, Ted K S Ng, Chinedu Udeh-Momoh, Catherine Ajalo, Kumar B Rajan, Anja Hviid Simonsen, Nicholas Ashton, Stefano Tamburin, Gorka Orive, Irene Esteban-Cornejo, Patricio Solis-Urra, Marcos Olvera-Rojas, Robert A Rissman, David Koh, Wayne Leifert, Robert Jenkins
Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association
2025;21(2):e14420
PMID: 39737743
Abstract
There is a pressing need for accessible biomarkers with high diagnostic accuracy for Alzheimer's disease (AD) diagnosis to facilitate widespread screening, particularly in underserved groups. Saliva is an emerging specimen for measuring AD biomarkers, with distinct contexts of use that could complement blood and cerebrospinal fluid and detect various analytes. An interdisciplinary, international group of AD and related dementias (ADRD) researchers convened and performed a narrative review of published studies on salivary AD biomarkers. We critically appraised the current state of the literature, examining both consistencies and discrepancies in existing pre-analytical variables and methodologies. We discussed how various pre-analytical variables could influence the detection and quantification of salivary biomarkers, showed technologies available to standardize collection procedures, and proposed a standardized pre-analytical protocol to guide future studies on salivary AD biomarker examinations. We identified potential contexts of use, gaps, and priorities and proposed future research directions. HIGHLIGHTS: Given its non-invasive nature, wider accessibility, and cultural acceptability, particularly in low-resourced settings, saliva is a biofluid complementary to blood and CSF. Current salivary AD biomarker studies do not control for many confounding pre-analytical variables during the sampling process, potentially leading to inaccurate salivary biomarker readings and conclusions, contributing to conflicting findings. Reviewing the current literature, including the consistencies and non-consistencies observed in the existing parameters and methodologies, discussing how they can affect salivary AD biomarker detection and quantification. Proposing a standardized salivary pre-analytical protocol, identifying the gaps and prioritizations needed to move this area forward, proposing future directions and potential contexts of use.
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Address:
Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.; Edson College of Nursing and Health Education, Arizona State University, Phoenix, Arizona, USA.; School of Public Health Sciences, Wake Forest University School of Medicine, North Carolina, Medical Center Boulevard, Winston-Salem, North Carolina, USA.; Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.; Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Stockholm, Sweden.; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.; PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Darussalam, Brunei.; Danish Dementia Research Centre (DDRC), Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Molecular Diagnostic Solutions Group, Human Health Program, Commonwealth Scientific and Industrial Research Organisation (CSIRO) Health and Biosecurity, Adelaide, South Australia, Australia.; School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia.; Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.; Banner Health Foundation and Banner Alzheimer's Foundation, Phoenix, Arizona, USA.; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.; UK Dementia Research Institute at UCL, Maple House, London, UK.; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Science Park, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Physiology and Neuroscience and Alzheimer's Disease Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.; Family Medicine and Osteopathic Manipulative Medicine, Institute for Healthy Aging, Institute for Translational Research, Texas College of Osteopathic Medicine, UNT Health Science Center, Fort Worth, Texas, USA.; Geroa Diagnostics, Vitoria-Gasteiz, Vitoria-Gasteiz, Spain.; Neurobiology of Alzheimer's Disease Unit, Functional Unit for Research into Chronic Diseases, Instituto de Salud Carlos III, Madrid, Spain.; Network Centre for Biomedical Research in Neurodegenerative Diseases (CIBERNED), ISCIII, Fuencarral-El Pardo, Madrid, Spain.; NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.; Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain.; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Madrid, Spain.; University Institute for Regenerative Medicine and Oral Implantology-UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria-Gasteiz, Spain.; Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy.; Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain.; Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain.; Faculty of Education and Social Sciences, University of Andres Bello, Viña del Mar, Chile.; Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain.; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Granada, Spain.; Instituto de Investigación Biosanitaria ibs.GRANADA, Beiro, Granada, Spain.; University of Sao Paulo and Sao Leopoldo Mandic School of Medicine, São Paulo, São Paulo, Brazil.; Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.; Oasis Diagnostics® Corporation, Vancouver, Washington, USA.; Central South University, Changsha, Hunan, China.; RapidDx, Inc. Milwaukee, New Berlin, Wisconsin, USA.
Link outs
Free resources
Full Text Sources:
Medical:
Subscription / membership required