QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 29, 2005, 25(26):6213-6220; doi:10.1523/JNEUROSCI.0664-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (44) Citing Articles via Google Scholar Google Scholar Articles by Hartman, R. E. Articles by Holtzman, D. M. Search for Related Content PubMed PubMed Citation Articles by Hartman, R. E. Articles by Holtzman, D. M.

 Previous Article  |  Next Article 

Neurobiology of Disease
Treatment with an Amyloid- Antibody Ameliorates Plaque Load, Learning Deficits, and Hippocampal Long-Term Potentiation in a Mouse Model of Alzheimer's Disease

Richard E. Hartman,^1,2 Yukitoshi Izumi,² Kelly R. Bales,³ Steven M. Paul,³ David F. Wozniak,² and David M. Holtzman¹

Departments of ¹Neurology and ²Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, and ³Neuroscience Discovery Research, Eli Lilly and Company, Indianapolis, Indiana 46285

PDAPP transgenic mice overexpress a mutant form of human amyloid precursor protein under control of the platelet-derived growth factor promoter in CNS neurons that causes early onset, familial Alzheimer's disease in humans. These mice, on a mixed genetic background, have been shown to have substantial learning impairments from early ages, as well as an age-dependent decline in learning ability that has been hypothesized to be caused by amyloid- (A) accumulation. The goals of this study were to determine: (1) whether PDAPP mice on a pure C57BL/6 background develop more severe age-dependent learning deficits than wild-type mice; (2) if so, whether A accumulation accounts for the excessive decline in learning ability; and (3) whether the learning deficits are reversible, even after significant A deposition. At 4-6, 10-12, or 17-19 months of age, PDAPP and littermate wild-type mice on a C57BL/6 background were tested on a 5 week water maze protocol in which the location of the escape platform changed weekly, requiring the mice to repeatedly learn new information. PDAPP mice exhibited impaired spatial learning as early as 4 months (pre-A deposition), and the performance of both wild-type and PDAPP mice declined with age. However, PDAPP mice exhibited significantly greater deterioration with age. Direct evidence for the role of A accumulation in the age-related worsening in PDAPP mice was provided by the observation that systemic treatment over several weeks with the anti-A antibody 10D5 reduced plaque deposition, increased plasma A, improved hippocampal long-term potentiation, and improved behavioral performance in aged PDAPP mice with substantial A burden.

Key words: APP; amyloid; spatial; immunization; electrophysiology; neuropathology

---

Received Feb 18, 2005; revised April 16, 2005; accepted May 24, 2005.

This article has been cited by other articles:

				V. Boissonneault, M. Filali, M. Lessard, J. Relton, G. Wong, and S. Rivest Powerful beneficial effects of macrophage colony-stimulating factor on {beta}-amyloid deposition and cognitive impairment in Alzheimer's disease Brain, April 1, 2009; 132(4): 1078 - 1092. [Abstract] [Full Text] [PDF]

				B. L. Burgess, P. F. Parkinson, M. M. Racke, V. Hirsch-Reinshagen, J. Fan, C. Wong, S. Stukas, L. Theroux, J. Y. Chan, J. Donkin, et al. ABCG1 influences the brain cholesterol biosynthetic pathway but does not affect amyloid precursor protein or apolipoprotein E metabolism in vivo J. Lipid Res., June 1, 2008; 49(6): 1254 - 1267. [Abstract] [Full Text] [PDF]

				E. Head, V. Pop, V. Vasilevko, M. Hill, T. Saing, F. Sarsoza, M. Nistor, L.-A. Christie, S. Milton, C. Glabe, et al. A Two-Year Study with Fibrillar {beta}-Amyloid (A{beta}) Immunization in Aged Canines: Effects on Cognitive Function and Brain A{beta} J. Neurosci., April 2, 2008; 28(14): 3555 - 3566. [Abstract] [Full Text] [PDF]

				A. Majumdar, D. Cruz, N. Asamoah, A. Buxbaum, I. Sohar, P. Lobel, and F. R. Maxfield Activation of Microglia Acidifies Lysosomes and Leads to Degradation of Alzheimer Amyloid Fibrils Mol. Biol. Cell, April 1, 2007; 18(4): 1490 - 1496. [Abstract] [Full Text] [PDF]

				G. Chen, K. S. Chen, D. Kobayashi, R. Barbour, R. Motter, D. Games, S. J. Martin, and R. G. M. Morris Active {beta}-Amyloid Immunization Restores Spatial Learning in PDAPP Mice Displaying Very Low Levels of {beta}-Amyloid J. Neurosci., March 7, 2007; 27(10): 2654 - 2662. [Abstract] [Full Text] [PDF]

				C. M. Prada, M. Garcia-Alloza, R. A. Betensky, S. X. Zhang-Nunes, S. M. Greenberg, B. J. Bacskai, and M. P. Frosch Antibody-Mediated Clearance of Amyloid-{beta} Peptide from Cerebral Amyloid Angiopathy Revealed by Quantitative In Vivo Imaging J. Neurosci., February 21, 2007; 27(8): 1973 - 1980. [Abstract] [Full Text] [PDF]

				S. C. Biswas, Y. Shi, J.-P. G. Vonsattel, C. L. Leung, C. M. Troy, and L. A. Greene Bim Is Elevated in Alzheimer's Disease Neurons and Is Required for {beta}-Amyloid-Induced Neuronal Apoptosis J. Neurosci., January 24, 2007; 27(4): 893 - 900. [Abstract] [Full Text] [PDF]

				M. J. Saganich, B. E. Schroeder, V. Galvan, D. E. Bredesen, E. H. Koo, and S. F. Heinemann Deficits in Synaptic Transmission and Learning in Amyloid Precursor Protein (APP) Transgenic Mice Require C-Terminal Cleavage of APP J. Neurosci., December 27, 2006; 26(52): 13428 - 13436. [Abstract] [Full Text] [PDF]

				C. L. Masters and K. Beyreuther Alzheimer's centennial legacy: prospects for rational therapeutic intervention targeting the A{beta} amyloid pathway Brain, November 1, 2006; 129(11): 2823 - 2839. [Abstract] [Full Text] [PDF]

				H.-W. Klafki, M. Staufenbiel, J. Kornhuber, and J. Wiltfang Therapeutic approaches to Alzheimer's disease Brain, November 1, 2006; 129(11): 2840 - 2855. [Abstract] [Full Text] [PDF]

				M. Maier, T. J. Seabrook, N. D. Lazo, L. Jiang, P. Das, C. Janus, and C. A. Lemere Short amyloid-beta (Abeta) immunogens reduce cerebral Abeta load and learning deficits in an Alzheimer's disease mouse model in the absence of an Abeta-specific cellular immune response. J. Neurosci., May 3, 2006; 26(18): 4717 - 4728. [Abstract] [Full Text] [PDF]

				E. B. Lee, L. Z. Leng, B. Zhang, L. Kwong, J. Q. Trojanowski, T. Abel, and V. M.-Y. Lee Targeting Amyloid-beta Peptide (Abeta) Oligomers by Passive Immunization with a Conformation-selective Monoclonal Antibody Improves Learning and Memory in Abeta Precursor Protein (APP) Transgenic Mice J. Biol. Chem., February 17, 2006; 281(7): 4292 - 4299. [Abstract] [Full Text] [PDF]

				S. Lesne and L. Kotilinek Amyloid Plaques and Amyloid-{beta} Oligomers: An Ongoing Debate J. Neurosci., October 12, 2005; 25(41): 9319 - 9320. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help