Age-progressing cognitive impairments and neuropathology in transgenic CRND8 mice.
Patients with Alzheimer's disease suffer from progressive cognitive impairments and show distinct post-mortem neuropathology, including beta-amyloid plaques. Transgenic (Tg) CRND8 mice carry a mutated human amyloid precursor protein gene and show age-related increases in beta-amyloid production and plaque deposition. It was previously reported that during the early stages of plaque deposition, Tg CRND8 mice demonstrated Morris maze impairments. However, it is unknown if Tg mice would be impaired at an earlier age prior to plaque deposition or more impaired at a later age with more extensive plaque deposition. In the current study, we describe Tg CRND8 age-progressing beta-amyloid neuropathology and cognitive abilities in greater detail. At all ages, Tg mice showed normal short-term memory in the Y-maze. Pre-plaque Tg and age-matched Non-Tg mice did not differ in learning the spatial Morris water maze. However, both early and late plaque Tg mice showed impairments during acquisition. In addition, although early plaque Tg mice performed well in the probe trial, late plaque Tg mice demonstrated impaired probe trial performance. Therefore compared to their Non-Tg littermates, Tg CRND8 mice demonstrate cognitive impairments that progressed with age and seemed to coincide with the onset of beta-amyloid plaque deposition.
Hyde
Lynn A
LA
Schering-Plough Research Institute, NJ 07033, Kenilworth, USA. lynn.hyde@spcorp.com
Kazdoba
Tatiana M
TM
Grilli
Mariagrazia
M
Lozza
Gianluca
G
Brusa
Rossella
R
Brussa
Rosella
R
Zhang
Qi
Q
Wong
Gwendolyn T
GT
McCool
Martha F
MF
Zhang
Lili
L
Parker
Eric M
EM
Higgins
Guy A
GA
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D058225:Plaque, Amyloid / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor