Enrichment of MCI and early Alzheimer's disease treatment trials using neurochemical and imaging candidate biomarkers.
AffiliationDiscipline of Psychiatry, School of Medicine, Trinity College, University of, Dublin, Trinity Center for Health Sciences, The Adelaide and Meath Hospital, incorporating the National Children's Hospital (AMiNCH), Tallaght, Dublin 24,, Ireland. email@example.com
MeSH*Alzheimer Disease/cerebrospinal fluid/pathology/radionuclide imaging
Cognition Disorders/cerebrospinal fluid/pathology/radionuclide imaging
Magnetic Resonance Imaging/methods
MetadataShow full item record
CitationJ Nutr Health Aging. 2009 Apr;13(4):373-5.
JournalThe journal of nutrition, health & aging
AbstractIn the earliest clinical stages of Alzheimer's Disease (AD), when symptoms are mild, clinical diagnosis will still be difficult. AD related molecular mechanisms precede symptoms. Biological markers can serve as early diagnostic indicators, as markers of preclinical pathological change, e.g. underlying mechanisms of action (MoA). Hypothesis based candidates are derived from structural and functional neuroimaging as well as from cerebrospinal fluid (CSF) and plasma. Unbiased exploratory approaches e.g. proteome analysis or rater independent fully automated imaging post-processing methods yield novel candidates. Recent progress in the validation of core feasible imaging and neurochemical biomarkers for functions such as early detection, classification, progression and prediction of AD is summarized. Single core feasible biomarkers can already be used to enrich populations at risk for AD and may be further enhanced using distinct combinations. Some biomarkers are currently in the process of implementation as primary or secondary outcome variables into regulatory guideline documents, e.g. regarding phase II in drug development programs as outcome measures in proof of concept or dose finding studies. There are specific biomarkers available depending on the hypothesized mechanism of action of a medicinal product, e.g. impact on the amyloidogenic cascade or on tauhyperphosphorylation. Ongoing large-scale international controlled multi-center trials will provide further validation of selected core feasible imaging and CSF biomarker candidates as outcome measures in early AD for use in phase III clinical efficacy trials. There is a need of rigorous co-development of biological trait- and statemarker candidates facilitated through planned synergistic collaboration between academic, industrial and regulatory partners.
- Core candidate neurochemical and imaging biomarkers of Alzheimer's disease.
- Authors: Hampel H, Bürger K, Teipel SJ, Bokde AL, Zetterberg H, Blennow K
- Issue date: 2008 Jan
- The Road Ahead to Cure Alzheimer's Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations.
- Authors: Cavedo E, Lista S, Khachaturian Z, Aisen P, Amouyel P, Herholz K, Jack CR Jr, Sperling R, Cummings J, Blennow K, O'Bryant S, Frisoni GB, Khachaturian A, Kivipelto M, Klunk W, Broich K, Andrieu S, de Schotten MT, Mangin JF, Lammertsma AA, Johnson K, Teipel S, Drzezga A, Bokde A, Colliot O, Bakardjian H, Zetterberg H, Dubois B, Vellas B, Schneider LS, Hampel H
- Issue date: 2014 Dec
- Biomarkers in clinical trials for neurodegenerative diseases: regulatory perspectives and requirements.
- Authors: Broich K, Weiergräber M, Hampel H
- Issue date: 2011 Dec
- Predicting cognitive decline in subjects at risk for Alzheimer disease by using combined cerebrospinal fluid, MR imaging, and PET biomarkers.
- Authors: Shaffer JL, Petrella JR, Sheldon FC, Choudhury KR, Calhoun VD, Coleman RE, Doraiswamy PM, Alzheimer’s Disease Neuroimaging Initiative.
- Issue date: 2013 Feb
- 2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception.
- Authors: Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Cedarbaum J, Green RC, Harvey D, Jack CR, Jagust W, Luthman J, Morris JC, Petersen RC, Saykin AJ, Shaw L, Shen L, Schwarz A, Toga AW, Trojanowski JQ, Alzheimer's Disease Neuroimaging Initiative.
- Issue date: 2015 Jun