title: Biomarkers for the Early Detection and Progression of Alzheimer's Disease.
abstract: The recent failures of potential disease-modifying drugs for Alzheimer's disease (AD) may reflect the fact that the enrolled participants in clinical trials are already too advanced to derive a clinical benefit. Thus, well-validated biomarkers for the early detection and accurate diagnosis of the preclinical stages of AD will be crucial for therapeutic advancement. The combinatorial use of biomarkers derived from biological fluids, such as cerebrospinal fluid (CSF), with advanced molecular imaging and neuropsychological testing may eventually achieve the diagnostic sensitivity and specificity necessary to identify people in the earliest stages of the disease when drug modification is most likely possible. In this regard, positive amyloid or tau tracer retention on positron emission tomography imaging, low CSF concentrations of the amyloid-β 1-42 peptide, high CSF concentrations in total tau and phospho-tau, mesial temporal lobe atrophy on magnetic resonance imaging, and temporoparietal/precuneus hypometabolism or hypoperfusion on 18F-fluorodeoxyglucose positron emission tomography have all emerged as biomarkers for the progression to AD. However, the ultimate AD biomarker panel will likely involve the inclusion of novel CSF and blood biomarkers more precisely associated with confirmed pathophysiologic mechanisms to improve its reliability for detecting preclinical AD. This review highlights advancements in biological fluid and imaging biomarkers that are moving the field towards achieving the goal of a preclinical detection of AD.
authors.affiliation: Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI, USA.|Department of Family Medicine, Michigan State University, Grand Rapids, MI, USA.|Hauenstein Neuroscience Center, Mercy Health Saint Mary's Hospital, Grand Rapids, MI, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Counts
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.|Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.|Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
authors.affiliation: Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI, USA.
authors.forename: Natosha
authors.initials: N
authors.lastname: Mercado
authors.affiliation: Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI, USA.
authors.forename: Irving E
authors.initials: IE
authors.lastname: Vega
authors.affiliation: Department of Neurobiology and Neurology, Barrow Neurological Institute, Phoenix, AZ, USA. elliott.mufson@dignityhealth.org.
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D018450:Disease Progression; D042241:Early Diagnosis; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D012680:Sensitivity and Specificity
chemical_list: D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D015415:Biomarkers; D018836:Inflammation Mediators
keywords: Alzheimer’s disease; Amyloid; Biomarker; Cerebrospinal fluid; Mild cognitive impairment; Positron emission tomography