Roher Alex E, Esh Chera, Kokjohn Tyler A, Kalback Walter, Luehrs Dean C, Seward James D, Sue Lucia I, Beach Thomas G
Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, 10515 W Santa Fe Dr, Sun City, AZ 85351, USA.
Arterioscler Thromb Vasc Biol. 2003 Nov 1;23(11):2055-62. doi: 10.1161/01.ATV.0000095973.42032.44. Epub 2003 Sep 25.
We conducted a quantitative investigation of brain arterial atherosclerotic damage and its relationship to sporadic Alzheimer's disease (AD).
Fifty-four consecutive autopsy cases, 32 AD and 22 nondemented control subjects, were examined to establish the degree of arterial stenosis. Vessel external and lumenal area measurements were taken from 3-mm arterial cross-sections to calculate a stenosis index. AD patient circle of Willis arteries possessed a significant degree of stenosis as a consequence of multiple and severe atherosclerotic lesions. These lesions were significantly more severe in AD cases than in age-matched controls (P<0.0001), and the number of stenoses and the index of occlusion (R=0.67; P<0.00001) were positively correlated. In addition, the index of stenosis significantly correlated with the following measures of AD neuropathological lesions: total plaque score, neuritic plaque score, neurofibrillary tangle score, Braak stage score, and white matter rarefaction score.
Our study reveals an association between severe circle of Willis atherosclerosis and sporadic AD that should be considered a risk factor for this dementia. These observations strongly suggest that atherosclerosis-induced brain hypoperfusion contributes to the clinical and pathological manifestations of AD.
我们对脑动脉粥样硬化损伤及其与散发性阿尔茨海默病(AD)的关系进行了定量研究。
对54例连续尸检病例进行检查,其中32例为AD患者,22例为非痴呆对照者,以确定动脉狭窄程度。从3毫米动脉横截面积测量血管外膜和管腔面积,计算狭窄指数。由于多处严重动脉粥样硬化病变,AD患者的Willis环动脉存在显著程度的狭窄。这些病变在AD病例中比年龄匹配的对照者严重得多(P<0.0001),狭窄数量与闭塞指数呈正相关(R=0.67;P<0.00001)。此外,狭窄指数与AD神经病理损伤的以下指标显著相关:总斑块评分、神经炎斑块评分、神经原纤维缠结评分、Braak分期评分和白质疏松评分。
我们的研究揭示了Willis环严重动脉粥样硬化与散发性AD之间的关联,应将其视为这种痴呆的一个危险因素。这些观察结果强烈表明,动脉粥样硬化引起的脑灌注不足导致了AD的临床和病理表现。