CALHM1在中国老年性痴呆人群中的突变类型及分布情况及其影响淀粉样蛋白代谢的分子机制

老年性痴呆是神经系统最常见的退行性疾病，其发病机制尚不明确。CALHM1是近期发现的可能与老年性痴呆发病有关的基因，有报道其P86L位点突变显著增加老年性痴呆的患病风险。在对其功能研究后发现，CALHM1能促进钙离子进入胞浆，并影响淀粉样蛋白的代谢。其突变体CALH.M1-P86L会引起β淀粉样蛋白水平上升及sAPPα下降，产生老年性痴呆的典型病理改变，但具体机制不明。钙依赖性的蛋白激酶C在淀粉样蛋白代谢中同样起着非常重要的调节作用。我们期望在以往工作的基础上，明确CALHM1在我国老年性痴呆患者中的突变类型和分布情况，研究CALHM1对细胞内钙离子浓度以及淀粉样蛋白代谢的调节，明确CALHM1-P86L突变后细胞内钙离子及蛋白激酶C的变化，进而探讨CALHM1通过蛋白激酶C影响淀粉样蛋白代谢的机制，从而为老年性痴呆的早期诊断及治疗提供线索。

Alzheimer's disease is the most common degenerative diseases of the nervous system,its pathogenesis is not clear. CALHM1 gene is a recently discovered gene which may be associated with Alzheimer's disease risk. Its P86L mutation significantly increased dementia risk.In addition, functional studies have found that CALHM1 as a calcium channel regulatory protein, its P86L mutation can affect the intracellular calcium concentration, and affects the metabolism of amyloid,but the mechanisms are unclear. Calcium dependent protein kinase C also plays a very important role in amyloid metabolism. Therefore, we expect to clarify the mutation type and distribution of CALHM1 in large population on the basis of previous work，and to explore the impact of the disease process.Study of CALHM1 on intracellular calcium concentration and the amyloid metabolism, and to clarify whether CALHM1-P86 mutation has influence on intracellular calcium and protein.kinase C in order to provide clues for the early diagnosis and treatment of Alzheimer's disease.