Presenilin 2 mutation accelerates the onset of impairment in trace eyeblink conditioning in a mouse model of Alzheimer's disease overexpressing human mutant amyloid precursor protein.
Missense mutations in 2 homologous genes, presenilin 1 (PS1) and presenilin 2 (PS2), cause dementia in a subset of early-onset familial Alzheimer's disease (FAD) pedigrees. The purpose of the present study was to investigate whether PS2 mutation accelerates the onset of trace eyeblink conditioning deficits in an Alzheimer's disease (AD) mouse model overexpressing human amyloid precursor protein (APP) with the Swedish mutation (K670N, M671L) (Tg2576 mice). For this purpose, a double-transgenic mouse (PS2Tg2576 mice) was produced by cross-breeding transgenic mice carrying human mutant PS2 (N141I) with Tg2576 mice. Long-trace interval (trace interval=500ms) eyeblink conditioning was tested in the PS2Tg2576 mice at ages 3, 4, 6, and 12 months. At 3 months, PS2Tg2576 mice exhibited normal acquisition of conditioned responses (CRs) during trace eyeblink conditioning, whereas trace conditioning was significantly impaired in PS2Tg2576 mice at ages 4, 6, and 12 months. In contrast, Tg2576 mice showed intact memory performance during trace conditioning at 4 months. This cross-sectional study clearly indicates that PS2 mutation significantly accelerates the onset of cognitive impairment in associative trace eyeblink memory.
Laboratory of Neurobiophysics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa 769-2193, Japan. kishimot@kph.bunri-u.ac.jp
Yasushi
Y
Kishimoto
Yutaka
Y
Kirino
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001767:Blinking; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000523:psychology*; D003214:Conditioning, Classical; D003430:Cross-Sectional Studies; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D053766:Presenilin-2 / Q000235:genetics*
D016564:Amyloid beta-Protein Precursor; D053766:Presenilin-2