目的： 报道4例经过脑脊液阿尔茨海默病（alzheimer's disease,AD）标志物和基因检测确诊的PS-1基因杂合突变的早发型AD患者临床表现和病情进展速度的差异。方法： 4例早发型痴呆患者通过痴呆家族史调查、神经心理学评估、神经系统查体、头颅MRI、脑脊液AD标志物和全外显子测序检测。结果： 此4例患者脑脊液AD标志物检测结果均符合ATN诊断框架，并且均经过基因全外显子测序确认为PS-1基因杂合突变，病例1为携带PS-1杂合突变位点（c.1186G>A），病例2和病例3携带PS-1基因同一杂合突变位点（c.791C>T），病例2同时携带额颞叶痴呆致病基因GRN基因杂合突变位点（c.329G>A），病例4携带PS-1基因杂合突变位点（c.265G>C），其中病例1、病例3和病例4均有痴呆家族史，病例2无痴呆家族史，病例2和病例3发病年龄相同，但是病例2的病情进展速度明显快于病例3，病例4的发病年龄为38岁，明显早于其家族其他成员痴呆发病年龄（50岁），病例4在儿童时期有脑震荡病史。 结论： PS-1基因突变所致早发型AD并非皆有痴呆家族史，从头突变并不少见，不同PS-1基因突变位点导致AD发病年龄不同，同一PS-1基因杂合突变导致AD发病年龄相同，但是后天因素包括教育程度、工作的复杂程度和脑外伤等也会对PS-1基因突变所致早发型AD的临床表现和进展速度产生显著影响。

Objective: To report the differences in clinical manifestations and disease progression rate of 4 patients with early-onset Alzheimer's disease (AD) who were diagnosed with PS-1 gene heterozygous mutation by cerebrospinal fluid markers and gene detection. Methods: Four patients with early-onset dementia were examined by family history investigation, neuropsychological evaluation, physical examination of nervous system, MRI of head, AD markers in cerebrospinal fluid and whole exon sequencing. Results: The detection results of AD markers in cerebrospinal fluid of these four patients were all in line with the ATN diagnostic framework, and all of them were confirmed to be PS-1 heterozygous mutation by gene whole exon sequencing. Case 1 carried PS-1 heterozygous mutation site (c.1186G>A), and cases 2 and 3 carried the same heterozygous mutation site of PS-1 gene (c.791C>T). Case 2 carries the heterozygous mutation site of GRN gene (c.329G>A), and case 4 carries the heterozygous mutation site of PS-1 gene (c.265G>C), among which case 1, case 3 and case 4 all have family history of dementia, case 2 has no family history of dementia, and the onset age of case 2 and case 3 is the same, but the progress speed of case 2 is obviously faster than that of case 3. The onset age of case 4 was 38 years old, which was significantly earlier than that of other members of his family (50 years old). Case 4 had a history of concussion in childhood. Conclusion: Not all early-onset AD caused by PS-1 gene mutation have a family history of dementia, and de novo mutation is not uncommon. Different PS-1 gene mutation sites lead to different onset ages of AD, and the same PS-1 gene heterozygous mutation leads to the same onset age of AD. However, acquired factors including education level, complexity of work and brain trauma will also have a significant impact on the clinical manifestations and progress rate of early-onset AD caused by PS-1 gene mutation.