Corder E H, Jelic V, Basun H, Lannfelt L, Valind S, Winblad B, Nordberg A
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Arch Neurol. 1997 Mar;54(3):273-7. doi: 10.1001/archneur.1997.00550150035013.
Recent findings of a reduced cerebral metabolic rate of glucose (CMRGlu) in at-risk relatives of patients with Alzheimer disease (AD) who carry the apolipoprotein E (APOE) epsilon 4 allele suggest a causative role for the E4 isoform in cognitive changes that lead to AD. It is not known whether epsilon 4 allele-associated deficits exist in patients with clinical AD.
To determine whether distinct patterns of cerebral hypometabolism exist in patients who carry the epsilon 4 allele.
Information on the CMRGlu and APOE genotype was available for 46 patients at a memory disorders clinic: 31 patients were diagnosed as having probable AD, 3 demented patients did not meet criteria for AD, and 12 patients had mild memory complaints. Positron emission tomography with the use of 18F-fludeoxyglucose was used to calculate the CMRGlu in the frontal and temporoparietal regions of the cortex. Estimates were standardized to the sensorimotor area of the cortex. Linear regression models were constructed to relate the APOE genotype to the CMRGlu, adjusting for cognitive status (ie, the Mini-Mental State Examination score).
Distinct patterns of the CMRGlu did not emerge for patients with different APOE genotypes. Bilateral deficits in the CMRGlu were found in the patients with AD. Left-right asymmetry was found in 8 of 12 patients with mild memory complaints: 7 of 8 had CMRGlu ratio less than 0.85 in the left side of the temporoparietal region of the cortex.
The APOE epsilon 4 allele does not appear to be associated with specific deficits in brain metabolism in patients with AD despite evidence that the epsilon 4 allele is associated with preclinical alterations. This finding is consistent with previous epidemiologic results that have demonstrated a higher risk for AD in carriers of the epsilon 4 allele, but no change in the rate of progression of AD.
近期研究发现，携带载脂蛋白E（APOE）ε4等位基因的阿尔茨海默病（AD）患者的高危亲属脑葡萄糖代谢率（CMRGlu）降低，这表明E4异构体在导致AD的认知变化中起因果作用。目前尚不清楚临床AD患者中是否存在ε4等位基因相关的缺陷。
确定携带ε4等位基因的患者是否存在不同的脑代谢减退模式。
在一家记忆障碍诊所，46例患者有CMRGlu和APOE基因型信息：31例患者被诊断为可能患有AD，3例痴呆患者不符合AD标准，12例患者有轻度记忆障碍主诉。使用18F-氟脱氧葡萄糖进行正电子发射断层扫描，以计算皮质额叶和颞顶叶区域的CMRGlu。估计值以皮质感觉运动区为标准进行标准化。构建线性回归模型，将APOE基因型与CMRGlu相关联，并根据认知状态（即简易精神状态检查评分）进行调整。
不同APOE基因型的患者未出现明显的CMRGlu模式。AD患者双侧CMRGlu降低。12例有轻度记忆障碍主诉的患者中有8例存在左右不对称：8例中的7例在皮质颞顶叶区域左侧的CMRGlu比值小于0.85。
尽管有证据表明ε4等位基因与临床前改变有关，但APOEε4等位基因似乎与AD患者的脑代谢特定缺陷无关。这一发现与先前的流行病学结果一致，即ε4等位基因携带者患AD的风险较高，但AD的进展速度没有变化。
