Enrichment of MCI and early Alzheimer's disease treatment trials using neurochemical and imaging candidate biomarkers.
Hampel, H Broich, K
Hampel, H
Broich, K
Advisors
Editors
Other Contributors
Date
2012-02-01T10:49:20Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
*Alzheimer Disease/cerebrospinal fluid/pathology/radionuclide imaging
Biological Markers/*analysis
Cognition Disorders/cerebrospinal fluid/pathology/radionuclide imaging
Early Diagnosis
Humans
Magnetic Resonance Imaging/methods
Positron-Emission Tomography/methods
Research Design
Biological Markers/*analysis
Cognition Disorders/cerebrospinal fluid/pathology/radionuclide imaging
Early Diagnosis
Humans
Magnetic Resonance Imaging/methods
Positron-Emission Tomography/methods
Research Design
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
In 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.
Language
eng
ISSN
1279-7707 (Print)
1279-7707 (Linking)
1279-7707 (Linking)
eISSN
ISBN
DOI
PMID
19300885