Mosconi L, Nacmias B, Sorbi S, De Cristofaro M T R, Fayazz M, Tedde A, Bracco L, Herholz K, Pupi A
Department of Clinical Pathophysiology, Nuclear Medicine Unit, University of Florence, Italy.
J Neurol Neurosurg Psychiatry. 2004 Mar;75(3):370-6. doi: 10.1136/jnnp.2003.014993.
Declines in brain glucose metabolism have been described early in Alzheimer's disease (AD), and there is evidence that a genetic predisposition to AD contributes to accelerate this process. The epsilon 4 (e4) allele of the apolipoprotein E (ApoE) gene has been implicated as a major risk factor in this process. The aim of this FDG-PET study was to assess the ApoE e4 dose related effect on regional cerebral glucose metabolism (METglc) in clinical AD patients, with statistical voxel based methods.
Eighty six consecutive mild to moderate AD patients included in the Network for Efficiency and Standardisation of Dementia Diagnosis database underwent FDG-PET scans at rest. PCR was used to determine the ApoE genotype. Patients were grouped as e4 non-carriers (n = 46), e3/e4 (n = 27) and e4/e4 (n = 13) carriers. A voxel-based mapping program was used to compare each AD subgroup with a database of 35 sex and age matched controls (p<0.001, corrected for cluster extent) and also to compare between the subgroups (p<0.001, uncorrected).
No difference was found as to age at examination, age at onset, sex, disease duration, educational level, or severity of dementia between AD subgroups. Compared with controls, all AD subgroups had equivalent METglc reductions in the precuneus, posterior cingulate, parietotemporal, and frontal regions. Direct comparisons between AD subgroups indicated that patients with at least one e4 allele had METglc reductions within additional associative and limbic areas compared with e4 non-carriers.
The present FDG-PET study showed different metabolic phenotypes related to the ApoE genotype in clinical AD patients, as revealed with voxel based statistical methods. The results suggest a generalised disorder in e4 carriers impairing metabolism globally, in addition to the more localised changes typical of AD patients.
在阿尔茨海默病（AD）早期就已发现脑葡萄糖代谢下降，且有证据表明AD的遗传易感性会加速这一过程。载脂蛋白E（ApoE）基因的ε4（e4）等位基因被认为是这一过程中的主要危险因素。本FDG-PET研究的目的是采用基于体素的统计学方法评估ApoE e4剂量对临床AD患者局部脑葡萄糖代谢（METglc）的影响。
连续纳入痴呆诊断数据库效率与标准化网络中的86例轻至中度AD患者，进行静息状态下的FDG-PET扫描。采用聚合酶链反应（PCR）确定ApoE基因型。患者分为e4非携带者（n = 46）、e3/e4携带者（n = 27）和e4/e4携带者（n = 13）。使用基于体素的映射程序将每个AD亚组与35名性别和年龄匹配的对照数据库进行比较（p<0.001，经簇范围校正），并在亚组之间进行比较（p<0.001，未校正）。
AD亚组在检查年龄、发病年龄、性别、病程、教育水平或痴呆严重程度方面未发现差异。与对照组相比，所有AD亚组在楔前叶、后扣带回、顶颞叶和额叶区域的METglc均有同等程度的降低。AD亚组之间的直接比较表明，与e4非携带者相比，至少携带一个e4等位基因的患者在额外的联合和边缘区域METglc降低。
本FDG-PET研究表明，基于体素的统计学方法显示，临床AD患者中与ApoE基因型相关的代谢表型不同。结果表明，除了AD患者典型的局部变化外，e4携带者存在影响整体代谢的全身性紊乱。
