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。
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 Medical 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,genetic testing,etc were analyzed using descriptive statistics.Three typical cases of EOAD:PS1 mutation,APP mutation,clinical manifestations of unknown 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 pathogenic genes PS1 and APP,17 cases(43.6%)with APOEε4 carrying rate,31 cases(79.5%)with medial temporal lobe atrophy,and 37 cases(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 ratio(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 mutation in the APP gene;No PS1,PS2,APP mutation genes was found in early-onset AD with unknown pathogenic gene mutations,and no dementia 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
作者
李海涛
杨伊姝
张伟
田园如画
李轩宇
LI Hai-tao;YANG Yi-shu;ZHANG Wei(Department of Neurology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)
出处
《临床和实验医学杂志》
2024年第14期1462-1467,共6页
Journal of Clinical and Experimental Medicine
基金
北京市医疗管理中心十大专业建设项目(编号:Q19051-07)
北京友谊医院科研启动基金(编号:yyqdkt2020-3)。
