Author/Editor		Salehi, Ahmad; Delcroix, Jean-Dominique; Belichenko, Pavel V; Stokin, Gorazd B
Title		Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration
Type		članek
Source		Neuron
Vol. and No.		Letnik 51, št. 1
Publication year		2006
Volume		str. 29-42
Language		eng
Abstract		Degeneration of basal forebrain cholinergic neurons (BFCNs) contributes to cognitive dysfunction in Alzheimer's disease (AD) and Down's syndrome (DS). We used Ts65Dn and Ts1Cje mouse models of DS to show that the increased dose of the amyloid precursor protein gene, App, acts to markedly decrease NGF retrograde transport and cause degeneration of BFCNs. NGF transport was also decreased in mice expressing wild-type human APP or a familial AD-linked mutant APP; while significant, the decreases were less marked and there was no evident degeneration of BFCNs. Because of evidence suggesting that the NGF transport defect was intra-axonal, we explored within cholinergic axons the status of early endosomes (EEs). NGF-containing EEs were enlarged in Ts65Dn mice and their App content was increased. Our study thus provides evidence for a pathogenic mechanism for DS in which increased expression of App, in the context of trisomy, causes abnormal transport of NGF and cholinergic neurodegeneration.
Descriptors		AMYLOID BETA-PROTEIN AMYLOID BETA-PROTEIN PRECURSOR ANIMALS AXONAL TRANSPORT CHOLINERGIC FIBERS DISEASE MODELS, ANIMAL DOWN SYNDROME ENDOSOMES MICE MICE, KNOCKOUT MICE, TRANSGENIC NERVE DEGENERATION