Departments of Psychology, Neurology and Neuroscience, Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Tucson, Arizona, USA.
California National Primate Center, University of California, Davis, Davis, California, USA.
J Comp Neurol. 2024 Sep;532(9):e25670. doi: 10.1002/cne.25670.
The brain changes of Alzheimer's disease (AD) include Abeta (Aβ) amyloid plaques ("A"), abnormally phosphorylated tau tangles ("T"), and neurodegeneration ("N"). These have been used to construct in vivo and postmortem diagnostic and staging classifications for evaluating the spectrum of AD in the "ATN" and "ABC" ("B" for Braak tau stage, "C" for Consortium to Establish a Registry for Alzheimer's Disease [CERAD] neuritic plaque density) systems. Another common AD feature involves cerebral amyloid angiopathy (CAA). We report the first experiment to examine relationships among cognition, brain distribution of amyloid plaques, CAA, tau/tangles, and magnetic resonance imaging (MRI)-determined volume changes (as a measure of "N") in the same group of behaviorally characterized nonhuman primates. Both ATN and ABC systems were applied to a group of 32 rhesus macaques aged between 7 and 33 years. When an immunohistochemical method for "T" and "B" was used, some monkeys were "triple positive" on ATN, with a maximum ABC status of A1B2C3. With silver or thioflavin S methods, however, all monkeys were classified as T-negative and B0, indicating the absence of mature neurofibrillary tangles (NFTs) and hence neuropathologically defined AD. Although monkeys at extremes of the ATN and ABC classifications, or with frequent CAA, had significantly lower scores on some cognitive tests, the lack of fully mature NFTs or dementia-consistent cognitive impairment indicates that fully developed AD may not occur in rhesus macaques. There were sex differences noted in the types of histopathology present, and only CAA was significantly related to gray matter volume.
阿尔茨海默病（AD）的大脑变化包括 Abeta（Aβ）淀粉样斑块（“A”）、异常磷酸化的 tau 缠结（“T”）和神经退行性变（“N”）。这些变化被用于构建体内和死后的诊断和分期分类，以评估 AD 在“ATN”和“ABC”（“B”代表 Braak tau 阶段，“C”代表 Consortium to Establish a Registry for Alzheimer's Disease [CERAD] 神经纤维斑块密度）系统中的谱。AD 的另一个常见特征涉及脑淀粉样血管病（CAA）。我们报告了第一个实验，该实验检查了同一组行为特征明显的非人类灵长类动物中的认知、大脑中淀粉样斑块的分布、CAA、tau/缠结以及磁共振成像（MRI）确定的体积变化（作为“N”的衡量标准）之间的关系。ATN 和 ABC 系统均应用于一组 32 只年龄在 7 至 33 岁之间的恒河猴。当使用 tau 和“B”的免疫组织化学方法时，一些猴子在 ATN 上呈“三重阳性”，ABC 状态最大为 A1B2C3。然而，用银或硫黄素 S 方法，所有猴子均被归类为 T 阴性和 B0，表明没有成熟的神经纤维缠结（NFT），因此没有神经病理学定义的 AD。尽管 ATN 和 ABC 分类的极端或频繁的 CAA 的猴子在某些认知测试中的得分显著较低，但完全成熟的 NFT 或与痴呆一致的认知障碍的缺乏表明，完全发展的 AD 可能不会发生在恒河猴中。在存在的组织病理学类型方面注意到了性别差异，只有 CAA 与灰质体积显著相关。
