Testing the Right Target and Right Drug at the Right Stage

被引:420
作者
Sperling, Reisa A. [1 ]
Jack, Clifford R., Jr. [2 ]
Aisen, Paul S. [3 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Alzheimer Res & Treatment,Brigham & Womens Ho, Boston, MA 02446 USA
[2] Mayo Clin, Dept Radiol, Rochester, MN 55902 USA
[3] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
关键词
MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; AMYLOID DEPOSITION; A-BETA; CSF BIOMARKERS; ASSOCIATION; MRI; RECOMMENDATIONS; PROGRESSION; PREDICTION;
D O I
10.1126/scitranslmed.3002609
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Alzheimer's disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Recent disappointing trial results at the dementia stage of AD have raised multiple questions about our current approaches to the development of disease-modifying agents. Converging evidence suggests that the pathophysiological process of AD begins many years before the onset of dementia. So why do we keep testing drugs aimed at the initial stages of the disease process in patients at the end-stage of the illness?
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页数:5
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共 36 条
[1]   Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease [J].
Bateman, Randall J. ;
Aisen, Paul S. ;
De Strooper, Bart ;
Fox, Nick C. ;
Lemere, Cynthia A. ;
Ringman, John M. ;
Salloway, Stephen ;
Sperling, Reisa A. ;
Windisch, Manfred ;
Xiong, Chengjie .
ALZHEIMERS RESEARCH & THERAPY, 2011, 3 (01)
[2]   A γ-Secretase Inhibitor Decreases Amyloid-β Production in the Central Nervous System [J].
Bateman, Randall J. ;
Siemers, Eric R. ;
Mawuenyega, Kwasi G. ;
Wen, Guolin ;
Browning, Karen R. ;
Sigurdson, Wendy C. ;
Yarasheski, Kevin E. ;
Friedrich, Stuart W. ;
DeMattos, Ronald B. ;
May, Patrick C. ;
Paul, Steven M. ;
Holtzman, David M. .
ANNALS OF NEUROLOGY, 2009, 66 (01) :48-54
[3]   Amyloid-β Associated Cortical Thinning in Clinically Normal Elderly [J].
Becker, J. Alex ;
Hedden, Trey ;
Carmasin, Jeremy ;
Maye, Jacqueline ;
Rentz, Dorene M. ;
Putcha, Deepti ;
Fischl, Bruce ;
Greve, Douglas N. ;
Marshall, Gad A. ;
Salloway, Stephen ;
Marks, Donald ;
Buckner, Randy L. ;
Sperling, Reisa A. ;
Johnson, Keith A. .
ANNALS OF NEUROLOGY, 2011, 69 (06) :1032-1042
[4]   Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment [J].
Brys, Miroslaw ;
Pirraglia, Elizabeth ;
Rich, Kenneth ;
Rolstad, Sindre ;
Mosconi, Lisa ;
Switalski, Remigiusz ;
Glodzik-Sobanska, Lidia ;
De Santi, Susan ;
Zinkowski, Ray ;
Mehta, Pankaj ;
Pratico, Domenico ;
Saint Louis, Leslie A. ;
Wallin, Anders ;
Blennow, Kaj ;
de Leon, Mony J. .
NEUROBIOLOGY OF AGING, 2009, 30 (05) :682-690
[5]  
Darby D. G., 2011, J ALZHEIMERS DI 0826
[6]   Cerebrospinal fluid tau/β-amyloid42 ratio as a prediction of cognitive decline in nondemented older adults [J].
Fagan, Anne M. ;
Roe, Catherine M. ;
Xiong, Chengjie ;
Mintun, Mark A. ;
Morris, John C. ;
Holtzman, David M. .
ARCHIVES OF NEUROLOGY, 2007, 64 (03) :343-349
[7]   PET imaging of amyloid deposition in patients with mild cognitive impairment [J].
Forsberg, Anton ;
Engler, Henry ;
Almkvist, Ove ;
Blomquist, Gunnar ;
Hagman, Goran ;
Wall, Anders ;
Ringheim, Anna ;
Langstrom, Bengt ;
Nordberg, Agneta .
NEUROBIOLOGY OF AGING, 2008, 29 (10) :1456-1465
[8]   Effects of Aβ immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease [J].
Fox, NC ;
Black, RS ;
Gilman, S ;
Rossor, MN ;
Griffith, SG ;
Jenkins, L ;
Koller, M .
NEUROLOGY, 2005, 64 (09) :1563-1572
[9]  
GomezIsla T, 1996, J NEUROSCI, V16, P4491
[10]   Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study [J].
Hansson, O ;
Zetterberg, H ;
Buchhave, P ;
Londos, E ;
Blennow, K ;
Minthon, L .
LANCET NEUROLOGY, 2006, 5 (03) :228-234