Rapid endocytosis, which takes only a few seconds, is widely observed in secretory cells. Although it is more efficient in recycling vesicles than slow clathrin-mediated endocytosis, its underlying mechanism, thought to be clathrin-independent, is largely unclear. Here we reported that cleavage of three SNARE proteins essential for exocytosis, including synaptobrevin, SNAP-25 and syntaxin, inhibited rapid endocytosis at the calyx of Held nerve terminal, suggesting the involvement of three SNARE proteins in rapid endocytosis. These SNARE proteins were also involved in slow endocytosis. In addition, SNAP-25 and syntaxin facilitated vesicle mobilization to the readily releasable pool, likely via their roles in endocytosis and/or exocytosis. We concluded that both rapid and slow endocytosis share the involvement of SNARE proteins. The dual role of three SNARE proteins in exo- and endocytosis suggests that SNARE proteins may be molecular substrates contributing to the exo-endocytosis coupling, which maintains exocytosis in secretory cells.

In the version of this Article originally published, the ' Anti-FLAG' label at the top-right of the right panel in Fig. 1b should have read ' Anti-GFP'. This error has now been corrected in the online versions of the Article.

phosphorylated tau antibodies tested. Method of fixation did not reveal amyloid plaques in young 3xTg-AD mice. Plaque deposition was sex dependent with females showing more plaques than males beginning at 9 months predominately in the subiculum and to a lesser degree in the hippocampus, cortex and amygdala. Conclusions: These results stress the importance of fixation method for the immunohistochemical visualization of tau epitopes in young 3xTg-AD mice, and that intraneuronal A␤ is not necessarily a precondition for the concurrent staining of tau epitopes in select brain regions in these mutant mice. Background: The loss of the cholinergic neurons of the Nucleus Basalis of Meynert in Alzheimer's disease (AD) patients has received a lot of attention since its discovery in the early 1970s, and most presently available pharmaceutical drugs for AD are thus designed to increase the transmission of the cholinergic system. Despite this intense focus on the cholinergic system in AD the reason for the cholinergic neuron loss is yet unknown. Many mouse models of AD have been generated, but few have shown to develop neuron degeneration. Furthermore, genetically modified mouse models of AD showing loss of cholinergic neurons are scarce. APP/PS1KI mice develop a neuron loss of about 50% in the CA1 of the hippocampal formation, a characteristic also found in AD patients, as well as behavioural deficits and a severe motor pathology at the age of 6 months. This study examined A␤ induced pathology and neuron loss in the cholinergic system of the double transgenic APP/PS1KI mouse model of AD. Methods: Immunohistochemistry, stereology, real time RT-PCR. Results: Swollen ChAT positive dystrophic neurites were found in proximity of plaques especially in the motor nuclei and the striatum, as well as in the cortex, hippocampal formation and thalamus corresponding to regions innervated by the cholinergic basal forebrain and pons complexes. Expression of the APP transgene was found in ChAT positive neurons of motor nuclei accompanied by robust intracellular A␤ accumulation, however, no neurons expressing the APP transgene and thus no neurons accumulating intracellular A␤ aggregates were found in either the forebrain or pons complexes or in the caudate putamen. Stereological quantification showed a 20-30% loss of ChAT positive neurons only in the motor nuclei Mo5 and 7N at 6 and 12 months in APP/PS1KI mice, as compared to PS1KI control mice. No loss of ChAT positive neurons was found in the cholinergic forebrain complex or in the caudate putamen. Conclusions: This study reports cholinergic cell loss correlating with the accumulation of intracellular A␤ in a mouse model of AD and thus supports the hypothesis of intracellular A␤ aggregates as an early pathological alteration triggering neurodegeneration in AD. P1-

No abstract

Alzheimer's disease (AD) is the most common form of dementia and is marked with cognitive impairment, cell loss, and reduction of life expectancy. Pathologically, senile plaque, beta-amyloid (Aβ) aggregates, and neurofibrillary tangle, tau aggregates, are the hallmark of the disease. Although genetics studies provide a causative link between the disease and Aβ accumulation, the interaction between Aβ and tau and its contribution to the