title: The critical need for defining preclinical biomarkers in Alzheimer's disease.
abstract: The increasing number of afflicted individuals with late-onset Alzheimer's disease (AD) poses significant emotional and financial burden on the world's population. Therapeutics designed to treat symptoms or alter the disease course have failed to make an impact, despite substantial investments by governments, pharmaceutical industry, and private donors. These failures in treatment efficacy have led many to believe that symptomatic disease, including both mild cognitive impairment (MCI) and AD, may be refractory to therapeutic intervention. The recent focus on biomarkers for defining the preclinical state of MCI/AD is in the hope of defining a therapeutic window in which the neural substrate remains responsive to treatment. The ability of biomarkers to adequately define the at-risk state may ultimately allow novel or repurposed therapeutic agents to finally achieve the disease-modifying status for AD. In this review, we examine current preclinical AD biomarkers and suggest how to generalize their use going forward.
authors.affiliation: Department of Neurology, Georgetown University Medical Center, Washington, DC, USA; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Massimo S
authors.initials: MS
authors.lastname: Fiandaca
authors.affiliation: Department of Neurology, University of Rochester School of Medicine, Rochester, NY, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Mapstone
authors.affiliation: Department of Oncology, Georgetown University Medical Center, Washington, DC, USA; Department of Biochemistry, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Amrita K
authors.initials: AK
authors.lastname: Cheema
authors.affiliation: Department of Neurology, Georgetown University Medical Center, Washington, DC, USA; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: hjf8@georgetown.edu.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D062706:Prodromal Symptoms
chemical_list: D015415:Biomarkers
keywords: Alzheimer's Disease Neuroimaging Initiative; Alzheimer's disease; Amyloid-β; Apolipoprotein E ε4; Asymptomatic; Cerebrospinal fluid biomarkers; Epigenomics; Metabolomics; Mild cognitive impairment; Neuroimaging biomarkers; Peripheral blood biomarkers; Preclinical; Proteomics; Tau; Transcriptomics