Early-onset versus late-onset Alzheimer's disease: the case of the missing APOE ε4 allele

被引:245
作者
van der Flier, Wiesje M. [1 ,2 ]
Pijnenburg, Yolande A. L. [1 ]
Fox, Nick C. [1 ,3 ]
Scheltens, Philip [1 ,3 ]
机构
[1] Vrije Univ Amsterdam, Alzheimer Ctr, Dept Neurol, Med Ctr, NL-1007 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands
[3] UCL, UCL Inst Neurol, Dementia Res Ctr, London, England
基金
英国医学研究理事会;
关键词
APOLIPOPROTEIN-E GENOTYPE; CEREBRAL GLUCOSE-METABOLISM; GENOME-WIDE ASSOCIATION; BRAIN ATROPHY; IDENTIFIES VARIANTS; PRESENILE-DEMENTIA; CLINICAL-DIAGNOSIS; COGNITIVE DECLINE; MAJOR SUBTYPES; CSF BIOMARKERS;
D O I
10.1016/S1474-4422(10)70306-9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Some patients with early-onset Alzheimer's disease (AD) present with a distinct phenotype. Typically, the first and most salient characteristic of AD is episodic memory impairment. A few patients, however, present with focal cortical, non-memory symptoms, such as difficulties with language, visuospatial, or executive functions. These presentations are associated with specific patterns of atrophy and frequently with a young age at onset. Age is not, however, the only determinant of phenotype; underlying factors, especially genetic factors, seem also to affect phenotype and predispose patients to younger or older age at onset. Importantly, patients with atypical early-onset disease seldom carry the APOE epsilon 4 allele, which is the most important risk factor for lowering the age of onset in patients with AD. Additionally, the APOE epsilon 4 genotype seems to predispose patients to vulnerability in the medial temporal areas, which leads to memory loss. Conversely, patients negative for the APOE epsilon 4 allele and with early-onset AD are more likely to be predisposed to vulnerability of cerebral networks beyond the medial temporal lobes. Other factors are probably involved in determining the pattern of atrophy, but these are currently unknown.
引用
收藏
页码:280 / 288
页数:9
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