Year: 2018
Type: review
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.
Source: Acta Neuropathologica
Authors: José Luis Molinuevo, Scott Ayton, Richard Batrla, Martin M. Bednar, Tobias Bittner, Jeffrey Cummings, Anne M. Fagan, Harald Hampel, Michelle M. Mielke, Alvydas Mikulskis, Sid O’Bryant, Philip Scheltens, Jeffrey Sevigny, Leslie M. Shaw, Holly D. Soares, Gary Tong, John Q. Trojanowski, Henrik Zetterberg, Kaj Blennow
Institutions: Universitat Pompeu Fabra, Pasqual Maragall Foundation, Hospital Clínic de Barcelona, Barcelonaβeta Brain Research Center, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, F. Hoffmann-La Roche AG, Roche Diagnostics International AG (Switzerland), Takeda (United States), Takeda (Japan), Cleveland Clinic, Lou Ruvo Brain Institute, Washington University in St. Louis, Centre National de la Recherche Scientifique, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, AXA Research Fund, Institut du Cerveau, Alzheimer Precision Medicine, Mayo Clinic, Biogen (United States), University of North Texas Health Science Center, Amsterdam UMC Location Vrije Universiteit Amsterdam, University of Pennsylvania, AbbVie (United States), Lundbeck (United States), Sahlgrenska University Hospital, UK Dementia Research Institute, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, University of Gothenburg
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
Awards: G1258743643, Chronic Traumatic Encephalopathy: Detection, Diagnosis, Course, and Risk Factors, G3103753459, Parkinson's Disease and Dementia, Health Disparities in Alzheimer's Disease and Mild Cognitive Impairment among Mexican Americans, Global Alzheimer's Platform Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's Disease, A Blood Test for Screening Into Alzheimer's Prevention Trials, Alzheimer's Disease Research Center, G7240651115, A Proinflammatory Endophenotype to Predict NSAID Treatment Response Alzheimer's Disease Clinical Trials, Institut de Neurosciences Translationnelles de Paris, G7811949961, Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - Resubmission, Antecedent Biomarkers for Alzheimer Disease: The Adult Children Study
OpenAlex ID: W2902155257