Intracellular Aß triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease.

Loss of cholinergic neurons in the Nucleus Basalis of Meynert in Alzheimer's disease (AD) patients was one of the first discoveries of neuron loss in AD. Despite an intense focus on the cholinergic system in AD, the reason for this cholinergic neuron loss is yet unknown. In the present study we examined Abeta-induced pathology and neuron loss in the cholinergic system of the bigenic APP/PS1KI mouse model. Expression of the APP transgene was found in ChAT-positive neurons of motor nuclei accompanied by robust intracellular Abeta accumulation, whereas no APP expressing neurons and thus no intracellular Abeta accumulation were found in neither the forebrain or pons complexes, nor in the caudate putamen. This expression pattern was used as a model system to study the effect of intra- and extracellular Abeta accumulation on neuron loss in the cholinergic system. Stereological quantification revealed a loss of ChAT-positive neurons in APP/PS1KI mice only in the motor nuclei Mo5 and 7N accumulating intracellular Abeta. This study supports the hypothesis of intracellular Abeta accumulation as an early pathological alteration contributing to cell death in AD.

Christensen DZ ，Bayer TA ，Wirths O 《-》

Transient intraneuronal A beta rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice.

Christensen DZ ，Kraus SL ，Flohr A ，Cotel MC ，Wirths O ，Bayer TA ... -  《-》

Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration.

Salehi A ，Delcroix JD ，Belichenko PV ，Zhan K ，Wu C ，Valletta JS ，Takimoto-Kimura R ，Kleschevnikov AM ，Sambamurti K ，Chung PP ，Xia W ，Villar A ，Campbell WA ，Kulnane LS ，Nixon RA ，Lamb BT ，Epstein CJ ，Stokin GB ，Goldstein LS ，Mobley WC ... -  《-》

Review on the APP/PS1KI mouse model: intraneuronal Abeta accumulation triggers axonopathy, neuron loss and working memory impairment.

Bayer TA ，Wirths O 《-》

Inflammatory changes are tightly associated with neurodegeneration in the brain and spinal cord of the APP/PS1KI mouse model of Alzheimer's disease.

Wirths O ，Breyhan H ，Marcello A ，Cotel MC ，Brück W ，Bayer TA ... -  《-》