Early development of social deficits in APP and APP-PS1 mice.
Mimicking relevant behavioral features of the human pathology is one of the most important challenges for animal models of neurological disorders including Alzheimer disease (AD). Indeed, the most popular genetic AD mouse lines bearing mutations of the amyloid precursor protein (APP) and presenilin 1 genes (PS1), often fail to present robust cognitive deficits or show them only at very advanced ages. It is therefore crucial to identify AD-like behavioral alterations which may reliably reflect the early stages of the pathology, thus permitting tests of more efficient early therapeutic interventions. Here, we demonstrated the very early expression of noncognitive AD-like symptoms, i.e., deficits in social interest, interaction and communication, in APP and APP-PS1 transgenic mice. Conversely, other noncognitive behaviors (sensori-motor gating) as well as cognitive abilities (spontaneous alternation) were unaltered in AD transgenics. Our data suggest that social deficits precede other neuropsychiatric and cognitive AD-like symptoms and can be employed as early markers of AD pathology in genetic mouse models.
University Bordeaux, INCIA, UMR 5287, F-33400 Talence, France.
Susanna
S
Pietropaolo
Pauline
P
Delage
Fanny
F
Lebreton
Wim E
WE
Crusio
Yoon H
YH
Cho
D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics*; D012919:Social Behavior
D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1