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 Signaling - Call For Papers

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 3 November 2006:
Vol. 314. no. 5800, pp. 777 - 781
DOI: 10.1126/science.1132814
Prev | Table of Contents | Next

Review

A Century of Alzheimer's Disease

Michel Goedert1* and Maria Grazia Spillantini2

One hundred years ago a small group of psychiatrists described the abnormal protein deposits in the brain that define the most common neurodegenerative diseases. Over the past 25 years, it has become clear that the proteins forming the deposits are central to the disease process. Amyloid-ß and tau make up the plaques and tangles of Alzheimer's disease, where these normally soluble proteins assemble into amyloid-like filaments. Tau inclusions are also found in a number of related disorders. Genetic studies have shown that dysfunction of amyloid-ß or tau is sufficient to cause dementia. The ongoing molecular dissection of the neurodegenerative pathways is expected to lead to a true understanding of disease pathogenesis.

1 Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 2QH, UK.
2 Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 2PY, UK.

* To whom correspondence should be addressed. E-mail: mg{at}mrc-lmb.cam.ac.uk

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Abnormally phosphorylated tau is associated with neuronal and axonal loss in experimental autoimmune encephalomyelitis and multiple sclerosis.
J. M. Anderson, D. W. Hampton, R. Patani, G. Pryce, R. A. Crowther, R. Reynolds, R. J. M. Franklin, G. Giovannoni, D. A. S. Compston, D. Baker, et al. (2008)
Brain 131, 1736-1748
   Abstract »    Full Text »    PDF »
Activation of the Amyloid Cascade in Apolipoprotein E4 Transgenic Mice Induces Lysosomal Activation and Neurodegeneration Resulting in Marked Cognitive Deficits.
H. Belinson, D. Lev, E. Masliah, and D. M. Michaelson (2008)
J. Neurosci. 28, 4690-4701
   Abstract »    Full Text »    PDF »
Protofibril Assemblies of the Arctic, Dutch, and Flemish Mutants of the Alzheimer's A{beta}1-40 Peptide.
N. L. Fawzi, K. L. Kohlstedt, Y. Okabe, and T. Head-Gordon (2008)
Biophys. J. 94, 2007-2016
   Abstract »    Full Text »    PDF »
Identification of Novel Genes That Modify Phenotypes Induced by Alzheimer's {beta}-Amyloid Overexpression in Drosophila.
W. Cao, H.-J. Song, T. Gangi, A. Kelkar, I. Antani, D. Garza, and M. Konsolaki (2008)
Genetics 178, 1457-1471
   Abstract »    Full Text »    PDF »
APOE {varepsilon}4 allele is associated with cognitive impairment in patients with multiple sclerosis.
J. Shi, C. B. Zhao, T. L. Vollmer, T. M. Tyry, and S. M. Kuniyoshi (2008)
Neurology 70, 185-190
   Abstract »    Full Text »    PDF »
Neuropathology for the Neuroradiologist: Plaques and Tangles.
F.J. Wippold II, N. Cairns, K. Vo, D.M. Holtzman, and J.C. Morris (2008)
AJNR Am. J. Neuroradiol. 29, 18-22
   Abstract »    Full Text »    PDF »
The tauopathy associated with mutation +3 in intron 10 of Tau: characterization of the MSTD family.
S. Spina, M. R. Farlow, F. W. Unverzagt, D. A. Kareken, J. R. Murrell, G. Fraser, F. Epperson, R. A. Crowther, M. G. Spillantini, M. Goedert, et al. (2008)
Brain 131, 72-89
   Abstract »    Full Text »    PDF »
Analysis of Tau Phosphorylation and Truncation in a Mouse Model of Human Tauopathy.
P. Delobel, I. Lavenir, G. Fraser, E. Ingram, M. Holzer, B. Ghetti, M. G. Spillantini, R. A. Crowther, and M. Goedert (2008)
Am. J. Pathol. 172, 123-131
   Abstract »    Full Text »    PDF »
Induction of Tau Pathology by Intracerebral Infusion of Amyloid- -Containing Brain Extract and by Amyloid- Deposition in APP x Tau Transgenic Mice.
T. Bolmont, F. Clavaguera, M. Meyer-Luehmann, M. C. Herzig, R. Radde, M. Staufenbiel, J. Lewis, M. Hutton, M. Tolnay, and M. Jucker (2007)
Am. J. Pathol. 171, 2012-2020
   Abstract »    Full Text »    PDF »
Chronoregulation by Asparagine Deamidation.
S. J. Weintraub and B. E. Deverman (2007)
Sci. STKE 2007, re7
   Abstract »    Full Text »    PDF »
Ex Vivo Occupancy of {gamma}-Secretase Inhibitors Correlates with Brain beta-Amyloid Peptide Reduction in Tg2576 Mice.
M. E. Goldstein, Y. Cao, T. Fiedler, J. Toyn, L. Iben, D. M. Barten, M. Pierdomenico, J. Corsa, C. V. C. Prasad, R. E. Olson, et al. (2007)
J. Pharmacol. Exp. Ther. 323, 102-108
   Abstract »    Full Text »    PDF »
Imaging the Abeta-Related Neurotoxicity of Alzheimer Disease.
H. Moreno, W. E. Wu, T. Lee, A. Brickman, R. Mayeux, T. R. Brown, and S. A. Small (2007)
Arch Neurol 64, 1467-1477
   Abstract »    Full Text »    PDF »
A simple algorithm locates beta-strands in the amyloid fibril core of {alpha}-synuclein, Abeta, and tau using the amino acid sequence alone.
S. Zibaee, O. S. Makin, M. Goedert, and L. C. Serpell (2007)
Protein Sci. 16, 906-918
   Abstract »    Full Text »    PDF »
Apolipoprotein E-Containing Lipoproteins Protect Neurons from Apoptosis via a Signaling Pathway Involving Low-Density Lipoprotein Receptor-Related Protein-1.
H. Hayashi, R. B. Campenot, D. E. Vance, and J. E. Vance (2007)
J. Neurosci. 27, 1933-1941
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

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