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Science 4 October 1996:
Vol. 274. no. 5284, pp. 99 - 103
DOI: 10.1126/science.274.5284.99
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Reports

Correlative Memory Deficits, Abeta Elevation, and Amyloid Plaques in Transgenic Mice

Karen Hsiao, * Paul Chapman, Steven Nilsen, Chris Eckman, Yasuo Harigaya, Steven Younkin, Fusheng Yang, Greg Cole

Transgenic mice overexpressing the 695-amino acid isoform of human Alzheimer beta -amyloid (Abeta ) precursor protein containing a Lys670 rightarrow  Asn, Met671 rightarrow  Leu mutation had normal learning and memory in spatial reference and alternation tasks at 3 months of age but showed impairment by 9 to 10 months of age. A fivefold increase in Abeta (1-40) and a 14-fold increase in Abeta (1-42/43) accompanied the appearance of these behavioral deficits. Numerous Abeta plaques that stained with Congo red dye were present in cortical and limbic structures of mice with elevated amounts of Abeta . The correlative appearance of behavioral, biochemical, and pathological abnormalities reminiscent of Alzheimer's disease in these transgenic mice suggests new opportunities for exploring the pathophysiology and neurobiology of this disease.

K. Hsiao and S. Nilsen, Department of Neurology, UMHC Box 295, 420 Delaware Street, University of Minnesota, Minneapolis, MN 55455, USA.
P. Chapman, Physiology Unit, University of Wales, Cardiff CF1 3US, UK.
C. Eckman, Y. Harigaya, S. Younkin, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA.
F. Yang and G. Cole, GRECC, Veterans Administration Medical Center, Sepulveda, CA 91343, USA, and Departments of Medicine and Neurology, University of California, Los Angeles, CA 91343, USA.
*   To whom correspondence should be addressed.

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J. Biol. Chem. 281, 28079-28089
   Abstract »    Full Text »    PDF »
A Novel Phospholipid Derivative of Indomethacin, DP-155 [Mixture of 1-Steroyl and 1-Palmitoyl-2-{6-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido]hexanoyl}-sn-glycero-3-phosophatidyl Choline], Shows Superior Safety and Similar Efficacy in Reducing Brain Amyloid beta in an Alzheimer's Disease Model.
E. Dvir, J. E. Friedman, J. Y. Lee, J. Y. Koh, F. Younis, S. Raz, I. Shapiro, A. Hoffman, A. Dahan, G. Rosenberg, et al. (2006)
J. Pharmacol. Exp. Ther. 318, 1248-1256
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Amyloid-{beta} Vaccination: Testing the Amyloid Hypothesis?: Heads We Win, Tails You Lose!.
H.-g. Lee, X. Zhu, A. Nunomura, G. Perry, and M. A. Smith (2006)
Am. J. Pathol. 169, 738-739
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Matrix Metalloproteinase-9 Degrades Amyloid-beta Fibrils in Vitro and Compact Plaques in Situ.
P. Yan, X. Hu, H. Song, K. Yin, R. J. Bateman, J. R. Cirrito, Q. Xiao, F. F. Hsu, J. W. Turk, J. Xu, et al. (2006)
J. Biol. Chem. 281, 24566-24574
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NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease.
C. A. Colton, M. P. Vitek, D. A. Wink, Q. Xu, V. Cantillana, M. L. Previti, W. E. Van Nostrand, J. B. Weinberg, and H. Dawson (2006)
PNAS 103, 12867-12872
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Neuronal SIRT1 Activation as a Novel Mechanism Underlying the Prevention of Alzheimer Disease Amyloid Neuropathology by Calorie Restriction.
W. Qin, T. Yang, L. Ho, Z. Zhao, J. Wang, L. Chen, W. Zhao, M. Thiyagarajan, D. MacGrogan, J. T. Rodgers, et al. (2006)
J. Biol. Chem. 281, 21745-21754
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Arundic Acid Ameliorates Cerebral Amyloidosis and Gliosis in Alzheimer Transgenic Mice.
T. Mori, T. Town, J. Tan, N. Yada, Y. Horikoshi, J. Yamamoto, T. Shimoda, Y. Kamanaka, N. Tateishi, and T. Asano (2006)
J. Pharmacol. Exp. Ther. 318, 571-578
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Wild-type Presenilin 1 Protects against Alzheimer Disease Mutation-induced Amyloid Pathology.
R. Wang, B. Wang, W. He, and H. Zheng (2006)
J. Biol. Chem. 281, 15330-15336
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Phosphorylation of Amyloid Precursor Protein (APP) at Thr668 Regulates the Nuclear Translocation of the APP Intracellular Domain and Induces Neurodegeneration..
K.-A Chang, H.-S. Kim, T.-Y. Ha, J.-W. Ha, K. Y. Shin, Y. H. Jeong, J.-P. Lee, C.-H. Park, S. Kim, T.-K. Baik, et al. (2006)
Mol. Cell. Biol. 26, 4327-4338
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Endomorphin-2, an endogenous tetrapeptide, protects against A{beta}1-42 in vitro and in vivo.
V. Szegedi, G. Juhasz, E. Rozsa, G. Juhasz-Vedres, Z. Datki, L. Fulop, Z. Bozso, A. Lakatos, I. Laczko, T. Farkas, et al. (2006)
FASEB J 20, 1191-1193
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Reductions in levels of the Alzheimer's amyloid {beta} peptide after oral administration of ginsenosides.
F. Chen, E. A. Eckman, and C. B. Eckman (2006)
FASEB J 20, 1269-1271
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Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice..
D. M. Wilcock, J. Alamed, P. E. Gottschall, J. Grimm, A. Rosenthal, J. Pons, V. Ronan, K. Symmonds, M. N. Gordon, and D. Morgan (2006)
J. Neurosci. 26, 5340-5346
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