Nanoscale reorganisation of synaptic proteins in Alzheimer's disease.

AIMS: Synaptic strength depends strongly on the subsynaptic organisation of presynaptic transmitter release and postsynaptic receptor densities, and their alterations are expected to underlie pathologies. Although synaptic dysfunctions are common pathogenic traits of Alzheimer's disease (AD), it remains unknown whether synaptic protein nano-organisation is altered in AD. Here, we systematically characterised the alterations in the subsynaptic organisation in cellular and mouse models of AD. METHODS: We used immunostaining and super-resolution stochastic optical reconstruction microscopy imaging to quantitatively examine the synaptic protein nano-organisation in both Aß1-42-treated neuronal cultures and cortical sections from a mouse model of AD, APP23 mice. RESULTS: We found that Aß1-42-treatment of cultured hippocampal neurons decreased the synaptic retention of postsynaptic scaffolds and receptors and disrupted their nanoscale alignment to presynaptic transmitter release sites. In cortical sections, we found that while GluA1 receptors in wild-type mice were organised in subsynaptic nanoclusters with high local densities, receptors in APP23 mice distributed more homogeneously within synapses. This reorganisation, together with the reduced overall receptor density, led to reduced glutamatergic synaptic transmission. Meanwhile, the transsynaptic alignment between presynaptic release-guiding RIM1/2 and postsynaptic scaffolding protein PSD-95 was reduced in APP23 mice. Importantly, these reorganisations were progressive with age and were more pronounced in synapses in close vicinity of Aß plaques with dense cores. CONCLUSIONS: Our study revealed a spatiotemporal-specific reorganisation of synaptic nanostructures in AD and identifies dense-core amyloid plaques as the major local inductor in APP23 mice.

The evaluation of general practitioners' awareness/knowledge and adherence to the GOLD guidelines in a Shanghai suburb.

The aim of this study was to determine levels of awareness of basic knowledge concerning control and prevention of chronic obstructive pulmonary disease (COPD) among general practitioners (GPs) in a Shanghai suburb and to evaluate adherence to GOLD (COPD) guidelines in primary care. All 593 practitioners, including rural and urban community GPs at 15 primary care centers in the Songjiang district of Shanghai, were questioned, comprising 331 from urban communities and 262 from rural. Only 115 GPs (19.4%) understood that COPD is categorized into acute exacerbation and stable stages, and 328 GPs (55.3%) recognized that treatment for COPD patients was still required during stable stages. A total of 235 GPs (39.6%) knew that oxygen therapy should be administered for >15 h/d as regular home therapy. In 97 cases of stage III and IV COPD, only 1 patient had accepted long-term home oxygen therapy. Prescriptions that conformed with the GOLD recommendations occurred in approximately 8% of patients according to GOLD COPD severity staging. Basic knowledge of prevention and treatment of COPD was seriously lacking in GPs. Additional training is clearly needed.