TY - JOUR
T1 - Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020
AU - Hampel, Harald
AU - Lista, Simone
AU - Teipel, Stefan J.
AU - Garaci, Francesco
AU - Nisticò, Robert
AU - Blennow, Kaj
AU - Zetterberg, Henrik
AU - Bertram, Lars
AU - Duyckaerts, Charles
AU - Bakardjian, Hovagim
AU - Drzezga, Alexander
AU - Colliot, Olivier
AU - Epelbaum, Stéphane
AU - Broich, Karl
AU - Lehéricy, Stéphane
AU - Brice, Alexis
AU - Khachaturian, Zaven S.
AU - Aisen, Paul S.
AU - Dubois, Bruno
PY - 2014/4/15
Y1 - 2014/4/15
N2 - Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD.
AB - Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD.
UR - http://www.scopus.com/inward/record.url?scp=84897954102&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2013.11.009
DO - 10.1016/j.bcp.2013.11.009
M3 - Journal articles
C2 - 24275164
AN - SCOPUS:84897954102
SN - 0006-2952
VL - 88
SP - 426
EP - 449
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 4
ER -