title: Role of cerebrospinal fluid biomarkers in clinical trials for Alzheimer's disease modifying therapies.
abstract: Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) Aβ1-42, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Inha University School of Medicine, Incheon 400-712, Korea. ; Hypoxia-related Disease Research Center, Inha University School of Medicine, Incheon 400-712, Korea. ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Hypoxia-related Disease Research Center, Inha University School of Medicine, Incheon 400-712, Korea. ; Department of Anatomy, Inha University School of Medicine, Incheon 400-712, Korea.
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Ryoo
authors.affiliation: Department of Emergency Medicine, Inje University Ilsan Paik Hospital, Ilsan 411-706, Korea.
authors.forename: Dong Wun
authors.initials: DW
authors.lastname: Shin
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. ; Institute on Aging and Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. ; Institute on Aging and Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
keywords: Alzheimer's disease; Aβ1-42; Cerebrospinal fluid biomarker; Clinical trial; Tau