Josephs Keith A, Whitwell Jennifer L, Ahmed Zeshan, Shiung Maria M, Weigand Stephen D, Knopman David S, Boeve Bradley F, Parisi Joseph E, Petersen Ronald C, Dickson Dennis W, Jack Clifford R
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Ann Neurol. 2008 Feb;63(2):204-12. doi: 10.1002/ana.21223.
To test the hypothesis that beta-amyloid (Abeta) burden is associated with rates of brain atrophy.
Forty-five subjects who had been prospectively studied, died, and had an autopsy diagnosis of low, intermediate, or high probability of Alzheimer's disease who had two volumetric head magnetic resonance imaging scans were identified. Compact and total (compact + diffuse) Abeta burden was measured using a computerized image analyzer with software program to detect the proportion of gray matter occupied by Abeta. Visual ratings of Abeta burden were also performed. The boundary shift integral was used to calculate change over time in whole-brain and ventricular volume. All boundary shift integral results were annualized by adjusting for scan interval. Demographics, cognitive measures, clinical diagnoses, apolipoprotein E genotype, neurofibrillary tangle (NFT) pathology, and vascular lesion burden were determined.
There was no correlation between compact or total Abeta burden, or visual Abeta ratings, and rates of brain loss or ventricular expansion in all subjects. However, significant correlations were observed between rates of brain loss and age, Braak NFT stage, and change over time in cognitive measures. These features also correlated with rates of ventricular expansion. The rates of brain loss and ventricular expansion were greater in demented compared with nondemented subjects.
These findings suggest that rate of brain volume loss is not determined by the amount of insoluble Abeta in the gray matter.
检验β-淀粉样蛋白（Aβ）负荷与脑萎缩率相关的假说。
确定了45名经过前瞻性研究、死亡且尸检诊断为阿尔茨海默病低、中或高概率并进行过两次头颅容积磁共振成像扫描的受试者。使用配备软件程序的计算机图像分析仪测量紧密型和总（紧密型+弥漫型）Aβ负荷，以检测Aβ占据的灰质比例。还对Aβ负荷进行了视觉评分。边界位移积分用于计算全脑和脑室体积随时间的变化。所有边界位移积分结果均通过调整扫描间隔进行年化处理。确定了人口统计学特征、认知测量、临床诊断、载脂蛋白E基因型、神经纤维缠结（NFT）病理学和血管病变负荷。
在所有受试者中，紧密型或总Aβ负荷、视觉Aβ评分与脑萎缩率或脑室扩大之间均无相关性。然而，观察到脑萎缩率与年龄、Braak NFT分期以及认知测量随时间的变化之间存在显著相关性。这些特征也与脑室扩大率相关。与非痴呆受试者相比，痴呆受试者的脑萎缩率和脑室扩大率更高。
这些发现表明，脑容量损失率并非由灰质中不溶性Aβ的量决定。
