摘要
目的 探讨3种不同类型早发性阿尔茨海默病(EOAD)的临床、影像生物标志物及基因特点.方法 运用首都医科大学附属北京友谊医院医渡云临床数据平台,以"AD、AD源性轻度认知功能障碍"作为疾病名称关键词,限制年龄为＜65岁,检索时间从2018年8月至2024年1月.采用描述性统计对符合条件的所有病例从临床特点、生物学标志物、神经影像、基因检测等进行分析.总结并分析3种EOAD典型病例:PS1突变、APP突变、未知基因型患者的临床表现、头颅MR、糖代谢正电子发射计算机断层显像仪(PET)或Aβ-PET、生物学标志物、基因测序结果.结果 39例患者致病基因PS1、APP突变为3例(7.7％),APOEε4携带率为17例(43.6％),内侧颞叶萎缩为31例(79.5％),糖代谢PET主要在后扣带回37例(94.8％);额、顶叶皮层34例(87.1％)代谢性降低等.Aβ-PET阳性9例,显像剂主要摄取部位集中在额顶叶(100％).脑脊液Aβ42降低12例(100％),平均(393.07±90.86)pg/mL;Aβ42/Aβ40比值降低12 例(100％),平均 0.06±0.02;磷酸化 Tau 蛋白(p-Tau)升高 10 例(83.3％),平均(125.82±43.21)pg/mL.家族性PS1突变AD存在PSEN1 p.Tyr159Ser基因突变;APP突变AD存在APP基因有1个突变;未知致病基因突变早发性AD未发现PS1、PS2、APP突变基因,未发现痴呆相关风险基因突变.结论 EOAD以"情景记忆力障碍"为主要临床特征,需要结合结构头颅核磁、糖代谢PET或Aβ-PET、生物学标志物、基因检测等综合因素进行临床诊断.
Abstract
Objective To explore the clinical,imaging,biomarker,and genetic characteristics of three different types of early-onset Alzheimer's disease(EOAD).Methods Using the Yidu Cloud clinical data platform of Beijing Friendship Hospital affiliated with Capital Medi-cal University,the disease name keywords were"AD"and"mild cognitive impairment caused by AD".The age limit was＜65 years old,and the search period was from August 2018 to January 2024.All eligible cases based on clinical characteristics,biological markers,neuroimaging,genet-ic testing,etc were analyzed using descriptive statistics.Three typical cases of EOAD:PS1 mutation,APP mutation,clinical manifestations of un-known genotype patients,head MR,glucose metabolism positron emission computed tomography(PET)or Aβ-PET,biological markers,gene sequencing results were summarized and analyzed.Results Among the 39 patients,there were 3 cases(7.7％)with mutations in the patho-genic genes PS1 and APP,17 cases(43.6％)with APOE ε4 carrying rate,31 cases(79.5％)with medial temporal lobe atrophy,and 37 ca-ses(94.8％)with reduced glucose metabolism PET metabolism mainly located in the posterior cingulate gyrus;34 cases(87.1％)were found in the frontal and parietal cortex.Nine cases were positive for Aβ-PET,with the main uptake site concentrated in the frontal and parietal lobes(100％).12 cases(100％)showed a decrease in cerebrospinal fluid Aβ42,with an average of(393.07±90.86)pg/mL;The Aβ42/Aβ40 ra-tio(0.06±0.02)decreased in 12 cases(100％),and phosphorylated Tau protein(p-Tau)increased in 10 cases(83.3％),with an average of(125.82±43.21)pg/mL.Familial PS1 mutation AD was found PSEN1 p.Tyr159Ser gene mutation;APP mutation AD was found one muta-tion in the APP gene;No PS1,PS2,APP mutation genes was found in early-onset AD with unknown pathogenic gene mutations,and no demen-tia related risk gene mutations was found.Conclusion The main clinical feature of EOAD is"situational memory impairment",which requires a combination of structural head MRI,glucose metabolism PET or Aβ-PET,biological markers,genetic testing,and other comprehensive factors for clinical diagnosis.
基金项目
北京市医疗管理中心十大专业建设项目(Q19051-07)
北京友谊医院科研启动基金(yyqdkt2020-3)
NETL
NSTL
万方数据