一、参加单位

截止到2014年12月份，该项目在全国设立7个研究中心，分布在北京、上海、重庆、山东、陕西、辽宁等地区。

二、家系收集进展

家族性阿尔茨海默病家系遍布全国各地，本中心派遣研究人员奔赴广东、江西、湖南、重庆、辽宁、河南及河北等地现场采集家系资料，免费进行神经心理测评及头颅检查，并留取血标本进行基因筛查。同时为外地家系来京提供免费检查及交通费、住宿费。目前已收集家族性阿尔茨海默病家系300余个，其中患者数达个及以上的家系约个。最大家系有患者例，家系成员百余人。家系登记汇总详见表1。

表1.CFAN家系收集情况汇总（截止到2015年3月1日）

已对20余个家系的100多位成员进行了免费的神经心理测评及头部MRI检查；为近100位成员免费进行了脑脊液生物标记物检查。组织专家明确诊断，为患者及家系成员进行免费诊疗指导和健康宣教。对200余个家系进行已知致病基因筛查和载脂蛋白E（apolipoprotein E, APOE）基因检查，并为家系成员进行遗传咨询。

三、目前正在开展的工作

全外显子测序目前已逐渐广泛用于寻找孟德尔遗传性疾病和其他复杂疾病的致病基因或易感基因。通过联合应用全外显子组测序和连锁分析方法，对家族性阿尔茨海默病家系进行研究可能会发现新的致病基因并进一步研究其致病机制。

全基因组关联研究（GWAS）的出现，使研究者有可能在全基因组范围内寻找易感基因，为探寻阿尔茨海默病的遗传机制带来了新的视角。目前亚洲尚缺乏阿尔茨海默病相关GWAS的报告，贾建平教授课题组前期已建立了大型AD患者临床资源库，目前已开始进行中国汉族人群阿尔茨海默病GWAS研究，以期发现阿尔茨海默病的遗传规律以及中国阿尔茨海默病人群新的风险基因。

四、基金支持

1.中加老年痴呆症及相关病症合作研究项目--阿尔茨海默病痴呆前阶段诊断标记物研究（81261120571）

2.北京市医管局扬帆计划--神经变性病（ZY201301）

3.北京脑重大疾病研究院国际转化神经科学联盟合作种子基金（PXM2014_014226_000006）

4.国自然重点--Abeta-淀粉样蛋白代谢相关基因启动子区变异在阿尔茨海默病发病机制中的作用（30830045）

5.国自然面上项目--家族性阿尔茨海默病脑库的建立与应用（30470615）

6.国自然面上项目--中国家族性阿尔茨海默病发病机制的实验研究（30370494）

7.北京自然基金重点项目--中国家族性阿尔茨海默病分子遗传学和易感基因功能研究（7071004）

8.北京脑重大疾病研究院科研促进项目（BIBDPXM2014_014226_000016）

9.重大新药创制、科技重大专项、十二五实施计划--中国神经精神疾病临床资源库的建立与应用（2011ZX09307-001-03）

10.十一五科技支撑计划课题轻度认知障碍诊断与干预研究（2006BAI02B01）

五、发表文章

1.Jia J*, Wang F, Wei C, Zhou A, Jia X, Li F, Tang M, Chu L, Zhou Y, Zhou C, Cui Y, Wang Q, Wang W, Yin P, Hu N, Zuo X, Song H, Qin W, Wu L, Li D, Jia L, Song J, Han Y, Xing Y, Yang P, Li Y, Qiao Y, Tang Y, Lv J, Dong X. The prevalence of dementia in urban and rural areas of China. Alzheimers Dement, 2014, 10(1): 1-9.

2. Jia J*, Zhou A, Wei C, Jia X, Wang F, Li F, Wu X, Mok V, Gauthier S, Tang M, Chu L, Zhou Y, Zhou C, Cui Y, Wang Q, Wang W, Yin P, Hu N, Zuo X, Song H, Qin W, Wu L, Li D, Jia L, Song J, Han Y, Xing Y, Yang P, Li Y, Qiao Y, Tang Y, Lv J, Dong X. The prevalence of mild cognitive impairment and its etiological subtypes in elderly Chinese. Alzheimers Dement, 2014,10(4):439-47.

3.Zhang Y, Lu L, Jia J*, Jia L, Geula C, Pei J, Xu Z, Qin W, Liu R, Li D, Pan N. A lifespan observation of a novel mouse model: in vivo evidence supports Aβ oligomer hypothesis. PLoS One, 2014, 9(1). e85885.

4.Wang X, Yang Y, Li C, Jia J. A novel KIAA0196 (SPG8) mutation in a Chinese family with spastic paraplegia. Chin Med J (Engl), 2014, 127(10): 1987-9.

5. Cong L, Jia J, Qin W, Ren Y, Sun Y. Genome-wide analysis of DNA methylation in an APP/PS1 mouse model of Alzheimer's disease. Acta Neurol Belg, 2014, 114(3): 195-206.

6.Lin F, Jia J*, Qin W. Enhancement of β-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, whichinvolves central insulin signaling in a transgenic mouse model. Neuro Report, 2014, 25(16):1289-95.

7.Wu L, Soder RB, Schoemaker D, Carbonnell F, Sziklas V, Rowley J, Mohades S, Fonov V, Bellec P, Dagher A, Shmuel A, Jia J, Gauthier S, Rosa-Neto P. Resting state executive control network adaptations in amnestic mild cognitive impairment. J Alzheimers Dis, 2014, 40(4): 993-1004.

8.Zhang J, Mao P, Jia J*. Plasma amyloid-β oligomers and soluble tumor necrosis factor receptors as potential biomarkers. Curr Alzheimer Res, 2014, 11(4):325-31.

9.Zhang J, Jia J*, Qin W, Wang S. Combination of plasma tumor necrosis factor receptors signaling proteins, beta-amyloid and apolipoprotein E for the detection of Alzheimer's disease. Neurosci Lett, 2013, 541:99-104.

10.Liang F, Jia J*, Wang S, Qin W, Liu R. Decreased plasma levels of soluble low density lipoprotein receptor-related protein-1 (sLRP) and the soluble form of the receptor for advanced glycation end products (sRAGE) in the clinical diagnosis of Alzheimer's disease. J Clin Neurosci, 2013, 20(3):357-61.

11.Yuan Q, Wang F, Xue S, Jia J*. Association of polymorphisms in the LRP1 and A2M genes with Alzheimer's disease in the Northern Chinese Han population. J Clin Neurosci, 2013, 20(2):253-6.

12.Xing Y, Jia J*, Ji XJ, Tian T. Estrogen associated gene polymorphisms and their interactions in the progress of Alzheimer's disease. Prog Neurobiol, 2013, 111:53-74.

13.Xing Y, Qin W, Li F, Jia X, Jia J*. Associations between sex hormones and cognitive and neuropsychiatric manifestations in vascular dementia (VaD). Arch Gerontol Geriatr,2013, 56(1):85-90.

14. Wu L, Rosa-Neto P, Hsiung GY, Sadovnick AD, Masellis M, Black SE, Jia J, Gauthier S. Early-onset familial Alzheimer's disease (EOFAD). Can J Neurol Sci, 2012, 39:436-45.

15. Li F, Jia X, Jia J*. The informant questionnaire on cognitive decline in the elderly individuals in screening mild cognitive impairment with or without functional impairment. J Geriatr Psychiatry Neurol, 2012, 25(4):227-32.

16.Wang S, Song J, Tan M, Albers K, Jia J*. Mitochondrial fission proteins in peripheral blood lymphocytes are potential biomarkers for Alzheimer's disease. Eur J Neurol, 2012,19(7):1015-22.

17.Wang F, Shu C, Jia L, Zuo X, Zhang Y, Zhou A, Qin W, Song H, Wei C, Zhang F, Hong Z, Tang M, Wang D, Jia J*. Exploration of 16 candidate genes identifies the association of IDE with Alzheimer's disease in Han Chinese. Neurobiol Aging, 2012, 33:1014. e1-9.

18.Xing Y, Wei C, Chu C, Zhou A, Li F, Wu L, Song H, Zuo X, Wang F, Qin W, Li D, Tang Y, Jia X, Jia J*. Stage-Specific Gender Differences in Cognitive and Neuropsychiatric Manifestations of Vascular Dementia. Am J Alzheimers Dis Other Demen, 2012, 27(6):433-8.

19. Han Y, Jia J*, Jia X, Qin W, Wang S. Combination of plasma biomarkers and clinical data for the detection of sporadic Alzheimer's disease. Neurosci Lett, 2012, 516(2):232-6.

20.Xing Y, Qin W, Li F, Jia X, Jia J*. Apolipoprotein E epsilon 4 Status Modifies the Effects of Sex Hormones on Neuropsychiatric Symptoms of Alzheimer's Disease. Dement Geriatr Cogn Disord, 2012,33(1):35-42.

21.Tan M, Wang S, Song J, Jia J*. Combination of p53(ser15) and p21/p21(thr145) in peripheral blood lymphocytes as potential Alzheimer's disease biomarkers. Neurosci Lett, 2012, 516(2):226-31.

22.Wang Y, Cheng Z, Qin W, Jia J*. Val97Leu mutant presenilin-1 induces tau hyperphosphorylation and spatial memory deficit in mice and the underlying mechanisms. J Neurochem, 2012, 121(1): 135-45.

23.Wu L, Rowley J, Mohades S, Leuzy A, Dauar MT, Shin M, Fonov V, Jia J, Gauthier S, Rosa-Neto P; Alzheimer's Disease Neuroimaging Initiative. Dissociation between brain amyloid deposition and metabolism in early mild cognitive impairment. PLoS One, 2012, 7(10): e47905.

24.Qin W, Jia L, Zhou A, Zuo X, Cheng Z, Wang F, Shi F, Jia J*. The -980C/G polymorphism in APH-1A promoter confers risk of Alzheimer's disease. Aging Cell, 2011, 10(4):711-9.

25.Cong L, Jia J*. Promoter polymorphisms which regulate ADAM9 transcription are protective against sporadic Alzheimer's disease. Neurobiol Aging, 2011, 32:54-62.

26.Lu J, Li Dan, Li F, Zhou A, Wang F, Zuo X, Jia X, Song H, Jia J*. Montreal Cognitive Assessment in Detecting Cognitive Impairment in Chinese Elderly Individuals: NSFC-REPORT-2012A Population-Based Study. J Geriatr Psychiatry Neurol, 2011, 24(4):184-90.

27.Han Y, Wang J, Zhao Z, Min B, Lu J, Li K, He Y, Jia J*. Frequency-dependent changes in the amplitude of low-frequency fluctuations in amnestic mild cognitive impairment: a resting-state fMRI study. Neuroimage, 2011, 55(1): 287-95.

28.Wang M, Jia J*. The interleukin-6 gene-572C/G promoter polymorphism modifies Alzheimer's risk in APOE epsilon 4 carriers. Neurosci Lett, 2010, 482(3):260-3.

29.Wang M, Li Y, Lu Y, Zuo X, Wang F, Zhang Z, Jia J*. The relationship between ADAM17 promoter polymorphisms and sporadic Alzheimer's disease in a Northern Chinese Han population. J Clin Neurosci, 2010, 17(10):1276-9.

30.Song H, Jia L, Zuo X, Jia J*. Association between haplotype-88G/25G in A2M with Alzheimer's disease. Neurosci Lett, 2010, 479(2):143-5.

31.Yu G, Jia J*. Is there an association of regulatory region polymorphism in the alpha-1-antichymotrypsin gene with sporadic Alzheimer's disease in the northern Han-Chinese population. J Clin Neurosci, 2010, 17(6):766-9.

32.Wang Min, Song Haiqing, Jia J*. Interleukin-6 receptor gene polymorphisms were associated with sporadic Alzheimer's disease in Chinese Han. Brain Res, 2010, 1327: 1-5.

33. Zhou X, Jia J*. P53-mediated G(1)/S checkpoint dysfunction in lymphocytes from Alzheimer's disease patients. Neurosci Lett, 2010, 468(3):320-5.

34.Wang S, Jia J*. Promoter Polymorphisms Which Modulate BACE1 Expression Are Associated With Sporadic Alzheimer's Disease. Am J Med Genet, 2010, 153B(1):159-66.

35.Ma Z, Han D, Zuo X, Wang F, Jia J*. Association between promoter polymorphisms of the nicastrin gene and sporadic Alzheimer's disease in North Chinese Han population. Neurosci Lett, 2009, 458(3):136-9.

36.Yuan Q, Zuo X, Jia J*. Association between promoter polymorphisms of vascular endothelial growth factor gene and sporadic Alzheimer's disease among Northern Chinese Han. Neurosci Lett, 2009, 457(3):133-6.

37.Lu Y, Wang M, Liu Z, Wang F, Da Y, Jia J*. No association between the promoter polymorphisms of PAI-1 gene and sporadic Alzheimer's disease in Chinese Han population. Neurosci Lett, 2009, 455(2):97-100.

38.Wang Y, Jia J*. Association between promoter polymorphisms in anterior pharynx-defective-1a and sporadic Alzheimer's disease in the North Chinese Han population. Neurosci Lett, 2009, 455(2):101-4.

39.Xue S, Jia L, Jia J*. Association between somatostatin gene polymorphisms and sporadic Alzheimer's disease in Chinese population. Neurosci Lett, 2009, 465(2):181-3.

40.Qin W, Jia J*. Down-regulation of insulin-degrading enzyme by presenilin 1 V97L mutant potentially underlies increased levels of amyloid beta 42. Eur J Neurosci, 2008, 27:2425-32.

41.Wei C, Jia J, Liang P, Guan Y. Ginsenoside Rg1 attenuates beta-amyloid-induced apoptosis in mutant PS1 M146L cells. Neurosci Lett, 2008, 443:145-9.

42.Fang B, Jia J*. Human neuroblastoma cells transfected with two Chinese presenilin 1 mutations are sensitized to trophic factor withdrawal and protected by insulin-like growth factor-1. Chin Med J, 2008, 121(10): 910-5.

43.Fang B, Jia J*. The effect of two newly Chinese presenilin-1 mutations on the sensitivity to trophic factor withdrawal in human neuroblastoma cells. Zhonghuayixuezazhi, 2007, 87(5): 336-40.

44.Fang B, Jia L, Jia J*. Chinese Presenilin-1 V97L mutation enhanced Abeta42 levels in SH-SY5Y neuroblastoma cells. Neurosci Lett, 2006, 406:33-7.

45.Jia J, Xu E, Shao Y, Jia J*, Sun Y, Li D. One novel presenilin-1 gene mutation in a Chinese pedigree of familial Alzheimer's disease. J Alzheimers Dis, 2005, 7:119-24.

46.刘艳，左秀美，贾建平*.去整合蛋白和金属蛋白酶10基因启动子区多态性与散发性阿尔茨海默病的关系.中华神经科杂志, 2012, 45(5):292-6.

47.贾建平*，王芬，袁泉，秦伟，唐毅，左秀美，韩阅.老年性痴呆早期的基因变异研究进展.生物化学与生物物理进展, 2012, 39(8):698-702.

48.左秀美，秦伟，周爱红，王芬，魏翠柏，贾建平*.RLM-RACE法确定胰岛素降解酶基因的转录起始位点.脑与神经疾病杂志, 2011, 19(6):401-3.

49.袁倩，贾建平*.中国北方汉族人群VEGF基因启动子区多态性的研究.脑与神经疾病杂志, 2011, 19(4):247-9.

50.衣立业，蒋传路，韩璎，贾建平*.血管型轻度认知功能障碍的影像学研究进展.华西医学,2011, 26(5):777-80.

51.程哲, 秦伟, 贾建平. 早老素-1 V97 L突变对人神经母细胞瘤细胞脑啡肽酶表达的影响.中华神经科杂志, 2011, 44(3):155-8.

52.秦伟, 周爱红, 左秀美, 王芬, 程哲, 贾建平. 转录因子GATA结合蛋白3在家族性阿尔茨海默病发病机制中的作用.中华神经科杂志, 2011, 44(3):159-62.

53.左秀美，王芬，秦伟，周爱红，贾建平*.胰岛素降解酶基因启动子区多态性与散发性阿尔茨海默病的关系.脑与神经疾病杂志, 2010, 18(3):179-83.

54.王芬, 方伯言, 贾建平. 稳定表达人野生型淀粉样前体蛋白细胞模型的建立与鉴定. 中国现代神经疾病杂志, 2009, 9(3):275-9.

55.许二赫, 贾建平. 早发性家族性Alzheimer病与载脂蛋白E基因相关性分析. 中国老年学杂志, 2006, 26(10):1312-4.

56.魏翠柏, 贾建平, 梁平. PS1基因突变转染细胞中α-分泌酶活性的实验研究. 北京中医药大学学报, 2006, 29(7):461-4.

57.方伯言, 贾建平. 早老素1基因突变与阿尔茨海默病病理变化的关系. 中国临床康复, 2005, 9(45):113-5.

58.邵延坤, 贾建平, 方伯言, 刘宪霜, 孙永馨, 董秀敏. 野生型与突变型PS1真核表达载体的构建及其在SH-SY5Y细胞中的表达. 中国实验诊断学, 2005, 9(6):853-6.

59.许二赫, 贾建平, 孙文君. Alzheimer病一家系四例. 中华医学遗传学杂志, 2003, 20(2):102.

60.贾建平, 许二赫. 家族性Alzheimer病淀粉样蛋白前体基因第16、17外显子的突变分析. 脑与神经疾病杂志, 2003, 11(4):201-4.

更新时间：2015-03-01