Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Jewish Home of San Francisco, San Francisco, California, USA.
FASEB J. 2018 Feb;32(2):888-893. doi: 10.1096/fj.201700731R. Epub 2018 Jan 4.
Interactions of the presynaptic proteins, neuronal pentraxin 2 (NPTX2) and neurexin 2α (NRXN2α), with their respective postsynaptic functional partners, GluA4-containing glutamate (AMPA4) receptor and neuroligin 1 (NLGN1), enhance excitatory synaptic activity in some areas of the hippocampus and cerebral cortex. As early damage of such excitatory circuits in the brain tissues of participants with Alzheimer's disease (AD) correlates with cognitive losses, plasma neuron-derived exosome (NDE) levels of these 2 pairs of specialized synaptic proteins were quantified to assess their biomarker characteristics. The NDE contents of all 4 proteins were decreased significantly in AD dementia ( n = 46), and diminished levels of AMPA4 and NLGN1 correlated with the extent of cognitive loss. In a preclinical period, 6-11 yr before the onset of dementia, the NDE levels of all but NPTX2 were significantly lower than those of matched controls, and levels of all proteins declined significantly with the development of dementia. Reductions in NDE levels of these specialized excitatory synaptic proteins may therefore be indicative of the extent of cognitive loss and may reflect progression of the severity of AD.-Goetzl, E. J., Abner, E. L., Jicha, G. A., Kapogiannis, D., Schwartz, J. B. Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer's disease.
突触前蛋白神经元五聚素 2（NPTX2）和神经连接蛋白 2α（NRXN2α）与其各自的突触后功能伴侣谷氨酸（AMPA4）受体和神经连接蛋白 1（NLGN1）结合，增强了海马体和大脑皮层某些区域的兴奋性突触活动。由于阿尔茨海默病（AD）患者脑组织中这些兴奋性回路的早期损伤与认知能力下降相关，因此量化了这 2 对特殊突触蛋白的血浆神经元衍生外泌体（NDE）水平，以评估其生物标志物特征。AD 痴呆症（n = 46）患者的所有 4 种蛋白的 NDE 含量均显著降低，AMPA4 和 NLGN1 水平降低与认知损失程度相关。在临床前阶段，即痴呆症发作前 6-11 年，除 NPTX2 外，所有蛋白的 NDE 水平均明显低于匹配对照组，并且随着痴呆症的发展，所有蛋白的水平均显著下降。这些特殊兴奋性突触蛋白的 NDE 水平降低可能表明认知损失的程度，并可能反映 AD 严重程度的进展。
