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.
The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,1Dennis J. Selkoe2*
It has been more than 10 years since it was first proposed that
the neurodegeneration in Alzheimer's disease (AD) may be causedby
deposition of amyloid -peptide (A) in plaques in brain tissue.According to the amyloid hypothesis, accumulation of A in thebrain
is the primary influence driving AD pathogenesis. The restof the
disease process, including formation of neurofibrillarytangles
containing tau protein, is proposed to result from animbalance between
A production and A clearance.
1 Laboratories of Neurogenetics, National
Institute on Aging, Bethesda, MD 20892, USA.
2 Center for Neurologic Diseases, Harvard Medical
School, Brigham and Women's Hospital, Boston, MA 02115, USA.
*
To whom correspondence should be addressed. E-mail:
selkoe{at}cnd.bwh.harvard.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
LETTERS
Stephen R. Robinson, Glenda M. Bishop;, Dennis J. Selkoe, and John Hardy (1 November 2002) Science298 (5595), 962.
[DOI: 10.1126/science.298.5595.962] |Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
AIP-1 ameliorates {beta}-amyloid peptide toxicity in a Caenorhabditis elegans Alzheimer's disease model.
W. M. Hassan, D. A. Merin, V. Fonte, and C. D. Link (2009)
Hum. Mol. Genet.
18, 2739-2747
|Abstract »|Full Text »|PDF »
Prostaglandin E2 Stimulates the Production of Amyloid-{beta} Peptides through Internalization of the EP4 Receptor.
T. Hoshino, T. Namba, M. Takehara, T. Nakaya, Y. Sugimoto, W. Araki, S. Narumiya, T. Suzuki, and T. Mizushima (2009)
J. Biol. Chem.
284, 18493-18502
|Abstract »|Full Text »|PDF »
Amyloid Reduction by Amyloid-{beta} Vaccination Also Reduces Mouse Tau Pathology and Protects from Neuron Loss in Two Mouse Models of Alzheimer's Disease.
D. M. Wilcock, N. Gharkholonarehe, W. E. Van Nostrand, J. Davis, M. P. Vitek, and C. A. Colton (2009)
J. Neurosci.
29, 7957-7965
|Abstract »|Full Text »|PDF »
The Butyrylcholinesterase K Variant Confers Structurally Derived Risks for Alzheimer Pathology{diamondsuit}.
E. Podoly, D. E. Shalev, S. Shenhar-Tsarfaty, E. R. Bennett, E. Ben Assayag, H. Wilgus, O. Livnah, and H. Soreq (2009)
J. Biol. Chem.
284, 17170-17179
|Abstract »|Full Text »|PDF »
Humanin Inhibits Neuronal Cell Death by Interacting with a Cytokine Receptor Complex or Complexes Involving CNTF Receptor {alpha}/WSX-1/gp130.
Y. Hashimoto, M. Kurita, S. Aiso, I. Nishimoto, and M. Matsuoka (2009)
Mol. Biol. Cell
20, 2864-2873
|Abstract »|Full Text »|PDF »
C. Nerelius, A. Sandegren, H. Sargsyan, R. Raunak, H. Leijonmarck, U. Chatterjee, A. Fisahn, S. Imarisio, D. A. Lomas, D. C. Crowther, et al. (2009)
PNAS
106, 9191-9196
|Abstract »|Full Text »|PDF »
Conditional Forebrain Inactivation of Nicastrin Causes Progressive Memory Impairment and Age-Related Neurodegeneration.
K. Tabuchi, G. Chen, T. C. Sudhof, and J. Shen (2009)
J. Neurosci.
29, 7290-7301
|Abstract »|Full Text »|PDF »
Formation of Hirano Bodies after Inducible Expression of a Modified Form of an Actin-Cross-Linking Protein.
J. F. Reyes, K. Stone, J. Ramos, and A. Maselli (2009)
Eukaryot. Cell
8, 852-857
|Abstract »|Full Text »|PDF »
Seeded growth of {beta}-amyloid fibrils from Alzheimer's brain-derived fibrils produces a distinct fibril structure.
A. K. Paravastu, I. Qahwash, R. D. Leapman, S. C. Meredith, and R. Tycko (2009)
PNAS
106, 7443-7448
|Abstract »|Full Text »|PDF »
Nitric Oxide Links Mitochondrial Fission to Alzheimer's Disease.
MMP-9 Sheds the {beta}2 Integrin Subunit (CD18) from Macrophages.
T. Vaisar, S. Y. Kassim, I. G. Gomez, P. S. Green, S. Hargarten, P. J. Gough, W. C. Parks, C. L. Wilson, E. W. Raines, and J. W. Heinecke (2009)
Mol. Cell. Proteomics
8, 1044-1060
|Abstract »|Full Text »|PDF »
Episodic memory loss is related to hippocampal-mediated {beta}-amyloid deposition in elderly subjects.
E. C. Mormino, J. T. Kluth, C. M. Madison, G. D. Rabinovici, S. L. Baker, B. L. Miller, R. A. Koeppe, C. A. Mathis, M. W. Weiner, W. J. Jagust, et al. (2009)
Brain
132, 1310-1323
|Abstract »|Full Text »|PDF »
A{beta}PP/APLP2 Family of Kunitz Serine Proteinase Inhibitors Regulate Cerebral Thrombosis.
F. Xu, M. L. Previti, M. T. Nieman, J. Davis, A. H. Schmaier, and W. E. Van Nostrand (2009)
J. Neurosci.
29, 5666-5670
|Abstract »|Full Text »|PDF »
Fibrillar amyloid-{beta} burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease.
E. M. Reiman, K. Chen, X. Liu, D. Bandy, M. Yu, W. Lee, N. Ayutyanont, J. Keppler, S. A. Reeder, J. B. S. Langbaum, et al. (2009)
PNAS
106, 6820-6825
|Abstract »|Full Text »|PDF »
Role and Therapeutic Potential of VEGF in the Nervous System.
C. Ruiz de Almodovar, D. Lambrechts, M. Mazzone, and P. Carmeliet (2009)
Physiol Rev
89, 607-648
|Abstract »|Full Text »|PDF »
Reviews: Current Concepts in Alzheimer's Disease: A Multidisciplinary Review.
L. Minati, T. Edginton, M. Grazia Bruzzone, and G. Giaccone (2009)
American Journal of Alzheimer's Disease and Other Dementias
24, 95-121
|Abstract »|PDF »
Successful Versus Failed Adaptation to High-Fat Diet-Induced Insulin Resistance: The Role of IAPP-Induced {beta}-Cell Endoplasmic Reticulum Stress.
A. V. Matveyenko, T. Gurlo, M. Daval, A. E. Butler, and P. C. Butler (2009)
Diabetes
58, 906-916
|Abstract »|Full Text »|PDF »
Hyperhomocysteinemia Increases {beta}-Amyloid by Enhancing Expression of {gamma}-Secretase and Phosphorylation of Amyloid Precursor Protein in Rat Brain.
C.-E Zhang, W. Wei, Y.-H. Liu, J.-H. Peng, Q. Tian, G.-P. Liu, Y. Zhang, and J.-Z. Wang (2009)
Am. J. Pathol.
174, 1481-1491
|Abstract »|Full Text »|PDF »
Intracerebroventricular amyloid-{beta} antibodies reduce cerebral amyloid angiopathy and associated micro-hemorrhages in aged Tg2576 mice.
D. R. Thakker, M. R. Weatherspoon, J. Harrison, T. E. Keene, D. S. Lane, W. F. Kaemmerer, G. R. Stewart, and L. L. Shafer (2009)
PNAS
106, 4501-4506
|Abstract »|Full Text »|PDF »
A Recessive Mutation in the APP Gene with Dominant-Negative Effect on Amyloidogenesis.
G. Di Fede, M. Catania, M. Morbin, G. Rossi, S. Suardi, G. Mazzoleni, M. Merlin, A. R. Giovagnoli, S. Prioni, A. Erbetta, et al. (2009)
Science
323, 1473-1477
|Abstract »|Full Text »|PDF »
Different Patterns of Cerebral Injury in Dementia With or Without Diabetes.
J. A. Sonnen, E. B. Larson, K. Brickell, P. K. Crane, R. Woltjer, T. J. Montine, and S. Craft (2009)
Arch Neurol
66, 315-322
|Abstract »|Full Text »|PDF »
Amyloid {beta}-Protein Assembly and Alzheimer Disease.
R. Roychaudhuri, M. Yang, M. M. Hoshi, and D. B. Teplow (2009)
J. Biol. Chem.
284, 4749-4753
|Full Text »|PDF »
Neural Stem Cells and Alzheimer's Disease: Challenges and Hope.
Zhongling Feng, Gang Zhao, and Lei Yu (2009)
American Journal of Alzheimer's Disease and Other Dementias
24, 52-57
|Abstract »|PDF »
O-Mannosylation is required for the solubilization of heterologously expressed human beta-amyloid precursor protein in Saccharomyces cerevisiae..
A. Murakami-Sekimata, K. Sato, K. Sato, A. Takashima, and A. Nakano (2009)
Genes Cells
14, 205-215
|Abstract »|Full Text »|PDF »
Microglial VEGF Receptor Response Is an Integral Chemotactic Component in Alzheimer's Disease Pathology.
J. K. Ryu, T. Cho, H. B. Choi, Y. T. Wang, and J. G. McLarnon (2009)
J. Neurosci.
29, 3-13
|Abstract »|Full Text »|PDF »
Do amyloid-lowering strategies work clinically?.
R. J. van Marum (2009)
Therapeutic Advances in Neurological Disorders
2, 3-6
|PDF »
Alzheimer disease: Time to improve its diagnosis and treatment.
S. SALLOWAY and S. CORREIA (2009)
Cleveland Clinic Journal of Medicine
76, 49-58
|Abstract »|Full Text »|PDF »
The Role of the Immune System in Alzheimer's Disease.
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 »
Amyloid-{beta} overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins.
X. Wang, B. Su, S. L. Siedlak, P. I. Moreira, H. Fujioka, Y. Wang, G. Casadesus, and X. Zhu (2008)
PNAS
105, 19318-19323
|Abstract »|Full Text »|PDF »
Consequence of A{beta} immunization on the vasculature of human Alzheimer's disease brain.
D. Boche, E. Zotova, R. O. Weller, S. Love, J. W. Neal, R. M. Pickering, D. Wilkinson, C. Holmes, and J. A. R. Nicoll (2008)
Brain
131, 3299-3310
|Abstract »|Full Text »|PDF »
Blocking A{beta}42 Accumulation Delays the Onset and Progression of Tau Pathology via the C Terminus of Heat Shock Protein70-Interacting Protein: A Mechanistic Link between A{beta} and Tau Pathology.
S. Oddo, A. Caccamo, B. Tseng, D. Cheng, V. Vasilevko, D. H. Cribbs, and F. M. LaFerla (2008)
J. Neurosci.
28, 12163-12175
|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 »
Dynamics of A{beta} Turnover and Deposition in Different {beta}-Amyloid Precursor Protein Transgenic Mouse Models Following {gamma}-Secretase Inhibition.
D. Abramowski, K.-H. Wiederhold, U. Furrer, A.-L. Jaton, A. Neuenschwander, M.-J. Runser, S. Danner, J. Reichwald, D. Ammaturo, D. Staab, et al. (2008)
J. Pharmacol. Exp. Ther.
327, 411-424
|Abstract »|Full Text »|PDF »
IL-4-Induced Selective Clearance of Oligomeric {beta}-Amyloid Peptide1-42 by Rat Primary Type 2 Microglia.
E. Shimizu, K. Kawahara, M. Kajizono, M. Sawada, and H. Nakayama (2008)
J. Immunol.
181, 6503-6513
|Abstract »|Full Text »|PDF »
Intramembrane Proteolysis by {gamma}-Secretase.
H. Steiner, R. Fluhrer, and C. Haass (2008)
J. Biol. Chem.
283, 29627-29631
|Abstract »|Full Text »|PDF »
Structural Classification of Toxic Amyloid Oligomers.
Novel Selective Allosteric Activator of the M1 Muscarinic Acetylcholine Receptor Regulates Amyloid Processing and Produces Antipsychotic-Like Activity in Rats.
C. K. Jones, A. E. Brady, A. A. Davis, Z. Xiang, M. Bubser, M. N. Tantawy, A. S. Kane, T. M. Bridges, J. P. Kennedy, S. R. Bradley, et al. (2008)
J. Neurosci.
28, 10422-10433
|Abstract »|Full Text »|PDF »
Nobiletin, a Citrus Flavonoid, Improves Memory Impairment and A{beta} Pathology in a Transgenic Mouse Model of Alzheimer's Disease.
H. Onozuka, A. Nakajima, K. Matsuzaki, R.-W. Shin, K. Ogino, D. Saigusa, N. Tetsu, A. Yokosuka, Y. Sashida, Y. Mimaki, et al. (2008)
J. Pharmacol. Exp. Ther.
326, 739-744
|Abstract »|Full Text »|PDF »
BACE1 Knock-Outs Display Deficits in Activity-Dependent Potentiation of Synaptic Transmission at Mossy Fiber to CA3 Synapses in the Hippocampus.
H. Wang, L. Song, F. Laird, P. C. Wong, and H.-K. Lee (2008)
J. Neurosci.
28, 8677-8681
|Abstract »|Full Text »|PDF »
Faster forgetting contributes to impaired spatial memory in the PDAPP mouse: Deficit in memory retrieval associated with increased sensitivity to interference?.
S. Daumas, J. Sandin, K. S. Chen, D. Kobayashi, J. Tulloch, S. J. Martin, D. Games, and R. G.M. Morris (2008)
Learn. Mem.
15, 625-632
|Abstract »|Full Text »|PDF »
The Amyloid-{beta} Rise and {gamma}-Secretase Inhibitor Potency Depend on the Level of Substrate Expression.
C. R. Burton, J. E. Meredith, D. M. Barten, M. E. Goldstein, C. M. Krause, C. J. Kieras, L. Sisk, L. G. Iben, C. Polson, M. W. Thompson, et al. (2008)
J. Biol. Chem.
283, 22992-23003
|Abstract »|Full Text »|PDF »
Presenilins: Members of the {gamma}-Secretase Quartets, But Part-Time Soloists Too.
Molecular dissection of ALS-associated toxicity of SOD1 in transgenic mice using an exon-fusion approach.
D. Han-Xiang, J. Hujun, F. Ronggen, Z. Hong, S. Yong, L. Erdong, H. Makito, C. D. C. Mauro, and S. Teepu (2008)
Hum. Mol. Genet.
17, 2310-2319
|Abstract »|Full Text »|PDF »
Glu332 in the Nicastrin Ectodomain Is Essential for {gamma}-Secretase Complex Maturation but Not for Its Activity.
L. Chavez-Gutierrez, A. Tolia, E. Maes, T. Li, P. C. Wong, and B. de Strooper (2008)
J. Biol. Chem.
283, 20096-20105
|Abstract »|Full Text »|PDF »
Abeta Predictor of Alzheimer Disease Symptoms.
C. F. Sephton and G. Yu (2008)
Arch Neurol
65, 875-876
|Full Text »|PDF »
Distinct Pools of {beta}-Amyloid in Alzheimer Disease-Affected Brain: A Clinicopathologic Study.
J. R. Steinerman, M. Irizarry, N. Scarmeas, S. Raju, J. Brandt, M. Albert, D. Blacker, B. Hyman, and Y. Stern (2008)
Arch Neurol
65, 906-912
|Abstract »|Full Text »|PDF »
Grape-Derived Polyphenolics Prevent A{beta} Oligomerization and Attenuate Cognitive Deterioration in a Mouse Model of Alzheimer's Disease.
J. Wang, L. Ho, W. Zhao, K. Ono, C. Rosensweig, L. Chen, N. Humala, D. B. Teplow, and G. M. Pasinetti (2008)
J. Neurosci.
28, 6388-6392
|Abstract »|Full Text »|PDF »
Protein Kinase C{epsilon} Binds Peripherin and Induces Its Aggregation, Which Is Accompanied by Apoptosis of Neuroblastoma Cells.
L. Sunesson, U. Hellman, and C. Larsson (2008)
J. Biol. Chem.
283, 16653-16664
|Abstract »|Full Text »|PDF »
Crystal Structure of an Active Form of BACE1, an Enzyme Responsible for Amyloid {beta} Protein Production.
H. Shimizu, A. Tosaki, K. Kaneko, T. Hisano, T. Sakurai, and N. Nukina (2008)
Mol. Cell. Biol.
28, 3663-3671
|Abstract »|Full Text »|PDF »
Neurogenesis and Alterations of Neural Stem Cells in Mouse Models of Cerebral Amyloidosis.
F. V. Ermini, S. Grathwohl, R. Radde, M. Yamaguchi, M. Staufenbiel, T. D. Palmer, and M. Jucker (2008)
Am. J. Pathol.
172, 1520-1528
|Abstract »|Full Text »|PDF »
Toll-Like Receptor 2 Acts as a Natural Innate Immune Receptor to Clear Amyloid {beta}1-42 and Delay the Cognitive Decline in a Mouse Model of Alzheimer's Disease.
K. L. Richard, M. Filali, P. Prefontaine, and S. Rivest (2008)
J. Neurosci.
28, 5784-5793
|Abstract »|Full Text »|PDF »
Potential Role of the Ubiquitin-Proteasome System in Atherosclerosis: Aspects of a Protein Quality Disease.
J. Herrmann, S. M. Soares, L. O. Lerman, and A. Lerman (2008)
J. Am. Coll. Cardiol.
51, 2003-2010
|Abstract »|Full Text »|PDF »
Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and A{beta} accumulation.
A. Muhammad, I. Flores, H. Zhang, R. Yu, A. Staniszewski, E. Planel, M. Herman, L. Ho, R. Kreber, L. S. Honig, et al. (2008)
PNAS
105, 7327-7332
|Abstract »|Full Text »|PDF »
Human Apolipoprotein E Redistributes Fibrillar Amyloid Deposition in Tg-SwDI Mice.
F. Xu, M. P. Vitek, C. A. Colton, M. L. Previti, N. Gharkholonarehe, J. Davis, and W. E. Van Nostrand (2008)
J. Neurosci.
28, 5312-5320
|Abstract »|Full Text »|PDF »
Platinum-based inhibitors of amyloid-{beta} as therapeutic agents for Alzheimer's disease.
K. J. Barnham, V. B. Kenche, G. D. Ciccotosto, D. P. Smith, D. J. Tew, X. Liu, K. Perez, G. A. Cranston, T. J. Johanssen, I. Volitakis, et al. (2008)
PNAS
105, 6813-6818
|Abstract »|Full Text »|PDF »
Islet Amyloid in Type 2 Diabetes, and the Toxic Oligomer Hypothesis.
L. Haataja, T. Gurlo, C. J. Huang, and P. C. Butler (2008)
Endocr. Rev.
29, 303-316
|Abstract »|Full Text »|PDF »
Role of Insulin Metabolism Disturbances in the Development of Alzheimer Disease: Mini Review.
B. Sabayan, F. Foroughinia, A. Mowla, and A. Borhanihaghighi (2008)
American Journal of Alzheimer's Disease and Other Dementias
23, 192-199
|Abstract »|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 »
Dynamics of the Microglial/Amyloid Interaction Indicate a Role in Plaque Maintenance.
T. Bolmont, F. Haiss, D. Eicke, R. Radde, C. A. Mathis, W. E. Klunk, S. Kohsaka, M. Jucker, and M. E. Calhoun (2008)
J. Neurosci.
28, 4283-4292
|Abstract »|Full Text »|PDF »
{beta}-Amyloid1-42 Induces Neuronal Death through the p75 Neurotrophin Receptor.
A. Sotthibundhu, A. M. Sykes, B. Fox, C. K. Underwood, W. Thangnipon, and E. J. Coulson (2008)
J. Neurosci.
28, 3941-3946
|Abstract »|Full Text »|PDF »
Stabilization of a {beta}-hairpin in monomeric Alzheimer's amyloid-{beta} peptide inhibits amyloid formation.
W. Hoyer, C. Gronwall, A. Jonsson, S. Stahl, and T. Hard (2008)
PNAS
105, 5099-5104
|Abstract »|Full Text »|PDF »
Characterization of Cullin-box Sequences That Direct Recruitment of Cul2-Rbx1 and Cul5-Rbx2 Modules to Elongin BC-based Ubiquitin Ligases.
N. Mahrour, W. B. Redwine, L. Florens, S. K. Swanson, S. Martin-Brown, W. D. Bradford, K. Staehling-Hampton, M. P. Washburn, R. C. Conaway, and J. W. Conaway (2008)
J. Biol. Chem.
283, 8005-8013
|Abstract »|Full Text »|PDF »
Lack of Pathology in a Triple Transgenic Mouse Model of Alzheimer's Disease after Overexpression of the Anti-Apoptotic Protein Bcl-2.
T. T. Rohn, V. Vyas, T. Hernandez-Estrada, K. E. Nichol, L.-A. Christie, and E. Head (2008)
J. Neurosci.
28, 3051-3059
|Abstract »|Full Text »|PDF »
Interaction of amyloid precursor protein with contactins and NgCAM in the retinotectal system.
M. Osterfield, R. Egelund, L. M. Young, and J. G. Flanagan (2008)
Development
135, 1189-1199
|Abstract »|Full Text »|PDF »
Retromer Sorting: A Pathogenic Pathway in Late-Onset Alzheimer Disease.
In Vivo {beta}-Secretase 1 Inhibition Leads to Brain A{beta} Lowering and Increased {alpha}-Secretase Processing of Amyloid Precursor Protein without Effect on Neuregulin-1.
S. Sankaranarayanan, E. A. Price, G. Wu, M.-C. Crouthamel, X.-P. Shi, K. Tugusheva, K. X. Tyler, J. Kahana, J. Ellis, L. Jin, et al. (2008)
J. Pharmacol. Exp. Ther.
324, 957-969
|Abstract »|Full Text »|PDF »
Progression of Amyloid Pathology to Alzheimer's Disease Pathology in an Amyloid Precursor Protein Transgenic Mouse Model by Removal of Nitric Oxide Synthase 2.
D. M. Wilcock, M. R. Lewis, W. E. Van Nostrand, J. Davis, M. L. Previti, N. Gharkholonarehe, M. P. Vitek, and C. A. Colton (2008)
J. Neurosci.
28, 1537-1545
|Abstract »|Full Text »|PDF »
Identification of {gamma}-Secretase Inhibitor Potency Determinants on Presenilin.
B. Zhao, M. Yu, M. Neitzel, J. Marugg, J. Jagodzinski, M. Lee, K. Hu, D. Schenk, T. Yednock, and G. Basi (2008)
J. Biol. Chem.
283, 2927-2938
|Abstract »|Full Text »|PDF »
Generation of A 38 and A 42 Is Independently and Differentially Affected by Familial Alzheimer Disease-associated Presenilin Mutations and {gamma}-Secretase Modulation.
R. M. Page, K. Baumann, M. Tomioka, B. I. Perez-Revuelta, A. Fukumori, H. Jacobsen, A. Flohr, T. Luebbers, L. Ozmen, H. Steiner, et al. (2008)
J. Biol. Chem.
283, 677-683
|Abstract »|Full Text »|PDF »
Suppression of in Vivo -Amyloid Peptide Toxicity by Overexpression of the HSP-16.2 Small Chaperone Protein.
V. Fonte, D. R. Kipp, J. Yerg III, D. Merin, M. Forrestal, E. Wagner, C. M. Roberts, and C. D. Link (2008)
J. Biol. Chem.
283, 784-791
|Abstract »|Full Text »|PDF »
Geranylgeranyl pyrophosphate stimulates {gamma}-secretase to increase the generation of A and APP-CTF{gamma}.
Y. Zhou, A. Suram, C. Venugopal, A. Prakasam, S. Lin, Y. Su, B. Li, S. M. Paul, and K. Sambamurti (2008)
FASEB J
22, 47-54
|Abstract »|Full Text »|PDF »
Chromosome 17 and 21 aneuploidy in buccal cells is increased with ageing and in Alzheimer's disease.
A Critical Function for -Amyloid Precursor Protein in Neuronal Migration Revealed by In Utero RNA Interference.
T. L. Young-Pearse, J. Bai, R. Chang, J. B. Zheng, J. J. LoTurco, and D. J. Selkoe (2007)
J. Neurosci.
27, 14459-14469
|Abstract »|Full Text »|PDF »
Signal Peptide Peptidase and {gamma}-Secretase Share Equivalent Inhibitor Binding Pharmacology.
L. G. Iben, R. E. Olson, L. A. Balanda, S. Jayachandra, B. J. Robertson, V. Hay, J. Corradi, C. V. C. Prasad, R. Zaczek, C. F. Albright, et al. (2007)
J. Biol. Chem.
282, 36829-36836
|Abstract »|Full Text »|PDF »
Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot Marie Tooth disease-linked mutations in NFL and HSPB1.
J. Zhai, H. Lin, J.-P. Julien, and W. W. Schlaepfer (2007)
Hum. Mol. Genet.
16, 3103-3116
|Abstract »|Full Text »|PDF »
In-cell Aggregation of a Polyglutamine-containing Chimera Is a Multistep Process Initiated by the Flanking Sequence.
Z. Ignatova, A. K. Thakur, R. Wetzel, and L. M. Gierasch (2007)
J. Biol. Chem.
282, 36736-36743
|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 »
Progesterone and Estrogen Regulate Alzheimer-Like Neuropathology in Female 3xTg-AD Mice.
J. C. Carroll, E. R. Rosario, L. Chang, F. Z. Stanczyk, S. Oddo, F. M. LaFerla, and C. J. Pike (2007)
J. Neurosci.
27, 13357-13365
|Abstract »|Full Text »|PDF »
Alzheimer's Disease Peptide Epitope Vaccine Reduces Insoluble But Not Soluble/Oligomeric A{beta} Species in Amyloid Precursor Protein Transgenic Mice.
I. Petrushina, A. Ghochikyan, M. Mktrichyan, G. Mamikonyan, N. Movsesyan, H. Davtyan, A. Patel, E. Head, D. H. Cribbs, and M. G. Agadjanyan (2007)
J. Neurosci.
27, 12721-12731
|Abstract »|Full Text »|PDF »
A Randomized Trial of Beta Carotene Supplementation and Cognitive Function in Men: The Physicians' Health Study II.
F. Grodstein, J. H. Kang, R. J. Glynn, N. R. Cook, and J. M. Gaziano (2007)
Arch Intern Med
167, 2184-2190
|Abstract »|Full Text »|PDF »
Involvement of Prostaglandin E2 in Production of Amyloid-beta Peptides Both in Vitro and in Vivo.
T. Hoshino, T. Nakaya, T. Homan, K.-i. Tanaka, Y. Sugimoto, W. Araki, M. Narita, S. Narumiya, T. Suzuki, and T. Mizushima (2007)
J. Biol. Chem.
282, 32676-32688
|Abstract »|Full Text »|PDF »
{beta}-Amyloid Modulation of Synaptic Transmission and Plasticity.
D. V. Venkitaramani, J. Chin, W. J. Netzer, G. K. Gouras, S. Lesne, R. Malinow, and P. J. Lombroso (2007)
J. Neurosci.
27, 11832-11837
|Full Text »|PDF »
Disease-modifying therapies for Alzheimer disease: Challenges to early intervention.
Moderate Reduction of {gamma}-Secretase Attenuates Amyloid Burden and Limits Mechanism-Based Liabilities.
T. Li, H. Wen, C. Brayton, F. M. Laird, G. Ma, S. Peng, L. Placanica, T. C. Wu, B. J. Crain, D. L. Price, et al. (2007)
J. Neurosci.
27, 10849-10859
|Abstract »|Full Text »|PDF »
Amyloid-beta reduction by memapsin 2 (beta-secretase) immunization.
W.-P. Chang, D. Downs, X.-P. Huang, H. Da, K.-M. Fung, and J. Tang (2007)
FASEB J
21, 3184-3196
|Abstract »|Full Text »|PDF »
FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease.
N. L. Foster, J. L. Heidebrink, C. M. Clark, W. J. Jagust, S. E. Arnold, N. R. Barbas, C. S. DeCarli, R. Scott Turner, R. A. Koeppe, R. Higdon, et al. (2007)
Brain
130, 2616-2635
|Abstract »|Full Text »|PDF »
APP at a glance.
M. S. Wolfe and S. Y. Guenette (2007)
J. Cell Sci.
120, 3157-3161
|Full Text »|PDF »
Partial Reduction of BACE1 Has Dramatic Effects on Alzheimer Plaque and Synaptic Pathology in APP Transgenic Mice.
L. McConlogue, M. Buttini, J. P. Anderson, E. F. Brigham, K. S. Chen, S. B. Freedman, D. Games, K. Johnson-Wood, M. Lee, M. Zeller, et al. (2007)
J. Biol. Chem.
282, 26326-26334
|Abstract »|Full Text »|PDF »
Low-density lipoprotein receptor-related protein promotes amyloid precursor protein trafficking to lipid rafts in the endocytic pathway.
I.-S. Yoon, E. Chen, T. Busse, E. Repetto, M. K. Lakshmana, E. H. Koo, and D. E. Kang (2007)
FASEB J
21, 2742-2752
|Abstract »|Full Text »|PDF »
Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter.
-peptide (A
