Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 3 November 2006:
Vol. 314. no. 5800, pp. 781 - 784
DOI: 10.1126/science.1132813

Review

100 Years and Counting: Prospects for Defeating Alzheimer's Disease

Erik D. Roberson and Lennart Mucke*

This week marks a century since the first description of Alzheimer's disease (AD). Despite approval of several drugs for AD, the disease continues to rob millions of their memories and their lives. Fortunately, many new therapies directly targeting the mechanisms underlying AD are now in the pipeline. Among the investigative AD therapies in clinical trials are several strategies to block pathogenic amyloid-ß peptides and to rescue vulnerable neurons from degeneration. Complementary but less mature strategies aim to prevent the copathogenic effects of apolipoprotein E and the microtubule-associated protein tau. New insights into selective neuronal vulnerability and the link between aging and AD may provide additional entry points for therapeutic interventions. The predicted increase in AD cases over the next few decades makes the development of better treatments a matter of utmost importance and urgency.

Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA.

* To whom correspondence should be addressed. E-mail: lmucke{at}gladstone.ucsf.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Preclinical Properties of 18F-AV-45: A PET Agent for A{beta} Plaques in the Brain.
S. R. Choi, G. Golding, Z. Zhuang, W. Zhang, N. Lim, F. Hefti, T. E. Benedum, M. R. Kilbourn, D. Skovronsky, and H. F. Kung (2009)
J. Nucl. Med. 50, 1887-1894
   Abstract »    Full Text »    PDF »
p75 reduces {beta}-amyloid-induced sympathetic innervation deficits in an Alzheimer's disease mouse model.
T. G. Bengoechea, Z. Chen, D. A. O'Leary, E. Masliah, and K.-F. Lee (2009)
PNAS 106, 7870-7875
   Abstract »    Full Text »    PDF »
Amyloid Goes Global.
I. Bezprozvanny (2009)
Science Signaling 2, pe16
   Abstract »    Full Text »    PDF »
PGC-1{alpha} Expression Decreases in the Alzheimer Disease Brain as a Function of Dementia.
W. Qin, V. Haroutunian, P. Katsel, C. P. Cardozo, L. Ho, J. D. Buxbaum, and G. M. Pasinetti (2009)
Arch Neurol 66, 352-361
   Abstract »    Full Text »    PDF »
Neprilysin Overexpression Inhibits Plaque Formation But Fails to Reduce Pathogenic A{beta} Oligomers and Associated Cognitive Deficits in Human Amyloid Precursor Protein Transgenic Mice.
W. J. Meilandt, M. Cisse, K. Ho, T. Wu, L. A. Esposito, K. Scearce-Levie, I. H. Cheng, G.-Q. Yu, and L. Mucke (2009)
J. Neurosci. 29, 1977-1986
   Abstract »    Full Text »    PDF »
First Demonstration of Cerebrospinal Fluid and Plasma A{beta} Lowering with Oral Administration of a {beta}-Site Amyloid Precursor Protein-Cleaving Enzyme 1 Inhibitor in Nonhuman Primates.
S. Sankaranarayanan, M. A. Holahan, D. Colussi, M.-C. Crouthamel, V. Devanarayan, J. Ellis, A. Espeseth, A. T. Gates, S. L. Graham, A. R. Gregro, et al. (2009)
J. Pharmacol. Exp. Ther. 328, 131-140
   Abstract »    Full Text »    PDF »
Mouse Models of Alzheimer's Dementia: Current Concepts and New Trends.
I. Torres-Aleman (2008)
Endocrinology 149, 5952-5957
   Abstract »    Full Text »    PDF »
Sequestration of Copper from {beta}-Amyloid Promotes Selective Lysis by Cyclen-Hybrid Cleavage Agents.
W.-h. Wu, P. Lei, Q. Liu, J. Hu, A. P. Gunn, M.-s. Chen, Y.-f. Rui, X.-y. Su, Z.-p. Xie, Y.-F. Zhao, et al. (2008)
J. Biol. Chem. 283, 31657-31664
   Abstract »    Full Text »    PDF »
Seladin-1 Is a Fundamental Mediator of the Neuroprotective Effects of Estrogen in Human Neuroblast Long-Term Cell Cultures.
P. Luciani, C. Deledda, F. Rosati, S. Benvenuti, I. Cellai, F. Dichiara, M. Morello, G. B. Vannelli, G. Danza, M. Serio, et al. (2008)
Endocrinology 149, 4256-4266
   Abstract »    Full Text »    PDF »
Enkephalin Elevations Contribute to Neuronal and Behavioral Impairments in a Transgenic Mouse Model of Alzheimer's Disease.
W. J. Meilandt, G.-Q. Yu, J. Chin, E. D. Roberson, J. J. Palop, T. Wu, K. Scearce-Levie, and L. Mucke (2008)
J. Neurosci. 28, 5007-5017
   Abstract »    Full Text »    PDF »
Efficient Inhibition of the Alzheimer's Disease {beta}-Secretase by Membrane Targeting.
L. Rajendran, A. Schneider, G. Schlechtingen, S. Weidlich, J. Ries, T. Braxmeier, P. Schwille, J. B. Schulz, C. Schroeder, M. Simons, et al. (2008)
Science 320, 520-523
   Abstract »    Full Text »    PDF »
Amyloid {beta} Protein Dimer-Containing Human CSF Disrupts Synaptic Plasticity: Prevention by Systemic Passive Immunization.
I. Klyubin, V. Betts, A. T. Welzel, K. Blennow, H. Zetterberg, A. Wallin, C. A. Lemere, W. K. Cullen, Y. Peng, T. Wisniewski, et al. (2008)
J. Neurosci. 28, 4231-4237
   Abstract »    Full Text »    PDF »
Inhibition of cytotoxicity and amyloid fibril formation by a D-amino acid peptide that specifically binds to Alzheimer's disease amyloid peptide.
K. Wiesehan, J. Stohr, L. Nagel-Steger, T. van Groen, D. Riesner, and D. Willbold (2008)
Protein Eng. Des. Sel. 21, 241-246
   Abstract »    Full Text »    PDF »
BEYOND AMYLOID: The Next Generation of Alzheimer's Disease Therapeutics.
G. R Seabrook, W. J. Ray, M. Shearman, and M. Hutton (2007)
Mol. Interv. 7, 261-270
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)