Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice

Science

Volumn 274, Issue 5284, 1996, Pages 99-102

  Hsiao, Karen ^a   Chapman, Paul ^b   Nilsen, Steven ^a   Eckman, Chris ^c   Harigaya, Yasuo ^c   Younkin, Steven ^c   Yang, Fusheng ^d,e   Cole, Greg ^d,e  

^a UNIVERSITY OF MINNESOTA   (United States)

^b CARDIFF UNIVERSITY   (United Kingdom)

^c MAYO CLINIC   (United States)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN;

ALZHEIMER DISEASE; AMINO ACID SUBSTITUTION; AMNESIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR DISORDER; CONTROLLED STUDY; DEMENTIA; ENZYME LINKED IMMUNOSORBENT ASSAY; LIMBIC CORTEX; MAZE TEST; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SENILE PLAQUE; TRANSGENIC MOUSE;

AGING; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BRAIN; BRAIN CHEMISTRY; LEARNING DISORDERS; MAZE LEARNING; MEMORY DISORDERS; MICE; MICE, TRANSGENIC; PEPTIDE FRAGMENTS; PSYCHOMOTOR PERFORMANCE;

ANIMALIA; MUS MUSCULUS;

EID: 0029742199     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.274.5284.99     Document Type: Article

References (32)

1. S. S. Mirra et al., Neurology 41, 479 (1991).
2. R. D. Terry et al., Ann. Neurol. 30, 572 (1991).
3. P. V. Arriagada, J. H. Growdon, E. T. Hedley-White, B. T. Hyman, Neurology 42, 631 (1992).
4. Z. S. Khachaturian, Arch. Neurol. 42, 1097 (1985).
5. E. H. Koo et al., Neuron 2, 97 (1990).
6. A. M. Goate et al., Nature 349, 704 (1991).
7. M.-C. Chartier-Harlin et al., ibid. 353, 844 (1991).
8. J. Murrell, M. Farlow, B. Ghetti, M. D. Benson, Science 254, 97 (1991).
9. L. Hendriks et al., Nature Genet. 1, 218 (1992).
10. M. Mullan et al., ibid., p. 345.
11. D. Games et al., Nature 373, 523 (1995).
12. P. M. Moran, L. S. Higgins, B. Cordell, P. C. Moser, Proc. Natl. Acad. Sci. U.S.A. 92, 5341 (1995).
13. L. S. Higgins, D. M. Holtzman, J. Rabin, W. C. Mobley, B. Cordell, Ann. Neurol. 35, 598 (1994).
14. K. K. Hsiao et al., Neuron 15, 1203 (1995).
15. M. R. Scott, R. Kohler, D. Foster, S. B. Prusiner, Protein Sci. 1, 985 (1992).
16. R. G. M. Morris, J. Neurosci. Methods 11, 47 (1984).
17. R. J. Douglas, in Spontaneous Alternation Behavior, W. N. Denber and L. L. Richman, Eds. (Springer-Verlag, New York, 1990), pp. 73-109.
18. The water maze was a circular pool (diameter 1 m) filled with water maintained at 29°C and made opaque by the addition of powdered milk. Mice were pretrained by swimming to a 12.7 cm by 12.7 cm Plexiglas platform that was submerged 1.5 cm beneath the surface of the water and placed at random locations within the pool. During pretraining, heavy curtains were drawn around the pool so that mice were unfamiliar with the extramaze room cues on the first day of spatial training. Spatial training consisted of four trials per day, each trial lasting until the mouse reached the platform or 60 s, whichever came first. After each trial, mice remained on the platform for 30 s. Twenty-four hours after the 12th and 24th trials, all mice were subjected to a probe trial in which they swam for 60 s in the pool with the platform removed. Mice were monitored by a camera mounted in the ceiling directly above the pool, and all trials were stored on videotape for subsequent analysis of platform crossings and percent time spent in each quadrant during probe trials. Visible-platform training-in the same pool but with a platform that was black, slightly larger (14.2 cm by 14.2 cm), and raised above the surface of the water-was given at least 24 hours after the second probe trial. The platform location was varied randomly from trial to trial to eliminate the potentially confounding contribution of extramaze spatial cues. In both visible-platform and hidden-platform versions, mice were placed in the pool facing toward the wall of the pool in one of seven randomly selected locations. The numbers of mice tested in the water maze were 12 transgenic and 12 controls at 2 months, 13 transgenic and 14 controls at 6 months, and 9 transgenic and 10 controls at 9 to 10 months of age.
19. The escape latency data were examined with a multifactor analysis of variance (ANOVA) including genotype (transgenic vs. control), age (2 months, 6 months, or 9 to 10 months), and training day (four trials per day). The ANOVA revealed significant main effects of genotype [F(1, 384) = 65,19, P < 0.0001], age [F(2, 384) = 7.64, P < 0.001], and trial block [F(5, 384) = 12.20, P < 0.0001]. Moreover, there was a significant interaction between genotype and age [F(2, 384) = 10.13, P < 0.0001], indicating that the transgene-induced impairment of escape latency increases with age.
20. All mice were also given a probe trial after 12 training trials (3 days at four trials per day). However, neither the transgenic nor the control mice had learned to search selectively after only 12 trials. The early probe trial was necessary because of the possibility of transient differences manifested only early in training, and because of the likelihood that we would have missed these differences because all behavioral tests were conducted blind to genotype. As none of the mice learned the task, there were no differences among any groups; for the sake of clarity, these data have not been presented graphically.
21. N. Suzuki et al., Science 264, 1336 (1994).
22. S. A. Gravina et al, J. Biol. Chem. 270, 7013 (1995).
23. T. C. Saido et al., ibid. 269, 15253 (1994).
24. K. S. Kim et al., Neurosci. Res. Commun, 7, 113 (1990).
25. K. S. Kim et al., ibid. 2, 121 (1988).
26. K. Mak, F. Yang, H. V. Vinters, S. A. Frautschy, G. M. Cole, Brain Res. 667, 138 (1994).
27. F. Yang, K. Mak, H. V. Vinters, S. A. Frautschy, G. M. Cole, Neuroreport 5, 2117 (1994).
28. T. C. Saido et al., Neuron 14, 457 (1995).
29. H. Puchtler, F. Sweat, M. Levine, J. Histochem. Cytochem. 10, 355 (1962).
30. M. Citron et al., Nature 360, 672 (1992).
31. D. Scheuner et al., Nature Med. 2, 864 (1996).
32. We thank J. Loh, A. Mariash, J. Meiners, W. Yunis, H. B. Clark, D. Borchelt, G. Carlson, and T. C. Saido for advice and technical help. Supported by NIH grants NS33249 (K.H.), AG9009 (G.C.), AG06656 (S.Y.), and AG12685 (S.Y.), NSF grant IBN9410131 (P.C.), the Alzheimer's Association (K.H. and S.Y.), the California State Department of Health (G.G.), the American Health Assistance Foundation (S.Y.), and the Neurosciences Education and Research Foundation (K.H.). Care of experimental animals described was in accordance with institutional guidelines.