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Reviews in the Neurosciences

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Neurologic and motor dysfunctions in APP transgenic mice

1 / Ken-ichiro Fukuchi2 / Catherine Strazielle3

1Faculté des Sciences, Département de Psychologie, Laboratoire ICONES, Université de Rouen, 76821 Mont-Saint-Aignan Cedex, France

2Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, P.O. Box 1649, Peoria, IL 61656, USA

3Faculté de Médecine, Laboratoire de Nutrition-Génétique et Exposition aux Risques Environnementaux, Université de Lorraine, INSERM U954, Service de Microscopie Electronique, 54500 Vandoeuvre-les-Nancy, France

Corresponding author: Robert Lalonde, Faculté des Sciences, Département de Psychologie, Laboratoire ICONES, Université de Rouen, 76821 Mont-Saint-Aignan Cedex, France

Citation Information: . Volume 23, Issue 4, Pages 363–379, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: 10.1515/revneuro-2012-0041, July 2012

Publication History

Received:
2012-03-19
Accepted:
2012-05-02
Published Online:
2012-07-29

Abstract

The discovery of gene mutations underlying autosomal dominant Alzheimer’s disease has enabled researchers to reproduce several hallmarks of this disorder in transgenic mice, notably the formation of Aβ plaques in brain and cognitive deficits. APP transgenic mutants have also been investigated with respect to survival rates, neurologic functions, and motor coordination, which are all susceptible to alteration in Alzheimer dementia. Several transgenic lines expressing human mutated or wild-type APP had higher mortality rates than non-transgenic controls with or without the presence of Aβ plaques. Mortality rates were also elevated in APP transgenic mice with vascular amyloid accumulation, thereby implicating cerebrovascular factors in the precocious death observed in all APP transgenic models. In addition, myoclonic jumping has been described in APP mutants, together with seizure activity, abnormal limb-flexion and paw-clasping reflexes, and motor coordination deficits. The neurologic signs resemble the myoclonic movements, epileptic seizures, pathological reflexes, and gait problems observed in late-stage Alzheimer’s disease.

Keywords: Alzheimer’s disease; epilepsy; motor coordination; myoclonus; paw-clasping; premature death

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