Cummings B J, Head E, Ruehl W, Milgram N W, Cotman C W
Brain Aging Institute, University of California, Irvine 92717-4540, USA.
Neurobiol Aging. 1996 Mar-Apr;17(2):259-68. doi: 10.1016/0197-4580(95)02060-8.
The aged canine displays many features that make it an excellent model for studying the progression of pathology in brain aging and linking these findings to learning, memory and other cognitive functions. Canines develop extensive beta-amyloid deposition within neurons and their synaptic fields, which appears to give rise to senile plaques. These plaques are primarily of the early diffuse subtype. Aged canines also exhibit accumulations of lipofuscin, cerebral vascular changes, dilation of the ventricles, and cytoskeletal changes. Neurofibrillary tangles (NFTs) are not present in the aged canine. Thus, the aged canine brain provides a suitable model for studying early degeneration normally considered to be pre-Alzheimer's. This supposition is also supported by behavioral data. We have found that the extent of beta-amyloid deposition correlates with a decline in select measures of cognitive function. These data provide the first evidence of a correlation between beta-amyloid accumulation and cognitive decline in the absence of NFTs. We summarize four lines of evidence that support using the aged canine as a model of human aging: (a) Aged canines develop aspects of neuropathology similar to that observed in aged humans; (b) Veterinarians have observed that many canines exhibit a clinical syndrome of age-related cognitive dysfunction; (c) Aged canines are deficient on a variety of neuropsychological tests of cognitive function; (d) The level of beta-amyloid accumulation correlates with cognitive dysfunction in the canine. These data indicate that the aged canine is a particularly useful model for studying age-related cognitive dysfunction (ARCD), early neuronal changes associated with aging, and the initial stages of senile plaque formation.
老年犬表现出许多特征，使其成为研究大脑衰老病理进展并将这些发现与学习、记忆及其他认知功能相联系的优秀模型。犬类在神经元及其突触区域会形成广泛的β-淀粉样蛋白沉积，这似乎会导致老年斑的形成。这些斑块主要是早期弥漫性亚型。老年犬还表现出脂褐素积累、脑血管变化、脑室扩张和细胞骨架变化。老年犬不存在神经原纤维缠结（NFTs）。因此，老年犬脑为研究通常被认为是阿尔茨海默病前期的早期退化提供了一个合适的模型。这一假设也得到了行为数据的支持。我们发现β-淀粉样蛋白沉积的程度与某些认知功能指标的下降相关。这些数据首次证明了在不存在NFTs的情况下β-淀粉样蛋白积累与认知衰退之间的相关性。我们总结了四条支持将老年犬作为人类衰老模型的证据：（a）老年犬出现的神经病理学方面与老年人类相似；（b）兽医观察到许多犬表现出与年龄相关的认知功能障碍临床综合征；（c）老年犬在各种认知功能的神经心理学测试中表现不佳；（d）β-淀粉样蛋白积累水平与犬的认知功能障碍相关。这些数据表明，老年犬是研究与年龄相关的认知功能障碍（ARCD）、与衰老相关的早期神经元变化以及老年斑形成初期的特别有用的模型。
