Altered auditory-evoked potentials in mice carrying mutated human amyloid precursor protein and presenilin-1 transgenes.
Transgenic mice carrying human APPswe and PS1-A264E transgenes (A/P mice) have elevated levels of the highly fibrillogenic amyloid Abeta(1-42) (Abeta) and develop amyloid plaques around the age of 9 months. Our aim was to find whether the gradual accumulation of Abeta in these mice can be detected with long-term recording of auditory-evoked potentials. The A/P double-mutant mice had impaired auditory gating and a tendency toward increased latency of the cortical N35 response, but these changes were not age-dependent between 7 and 11 months of age. In a control experiment that included also APP and PS1 single-mutant mice, the A/P double-mutant mice had weaker auditory gating than either APP or PS1 mice. In contrast, increased N35 latency was found in both A/P and APP mice compared with nontransgenic or PS1 mice. The Abeta40 and Abeta42 levels were robustly increased in A/P mice and Abeta40 moderately increased also in APP mice. Plaques were deposited only in A/P mice. We conclude that the impaired auditory gating is associated with the overproduction Abeta42 but does not reflect its amount. In contrast, increased N35 latency is related to the APP genotype independent of Abeta42 production.
Wang
J
J
Department of Neuroscience and Neurology, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland.
Ikonen
S
S
Gurevicius
K
K
Van Groen
T
T
Tanila
H
H
D000544:Alzheimer Disease / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D005838:Genotype; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1; D012995:Solubility
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1