Department of Pathology and Experimental Therapeutics, University of Barcelona, Barcelona, Spain.
J Alzheimers Dis. 2024;100(s1):S153-S164. doi: 10.3233/JAD-240389.
Senile plaques, mainly diffuse, and cerebral amyloid-β (Aβ) angiopathy are prevalent in the aging brain of non-human primates, from lemurs to non-human Hominidae. Aβ but not hyper-phosphorylated tau (HPtau) pathology is the common nominator proteinopathy of non-human primate brain aging. The abundance of Aβ in the aging primate brain is well tolerated, and the impact on cognitive functions is usually limited to particular tasks. In contrast, human brain aging is characterized by the early appearance of HPtau pathology, mainly forming neurofibrillary tangles, dystrophic neurites of neuritic plaques, and neuropil threads, preceding Aβ deposits by several decades and by its severity progressing from selected nuclei of the brain stem, entorhinal cortex, and hippocampus to the limbic system, neocortex, and other brain regions. Neurofibrillary tangles correlate with cognitive impairment and dementia in advanced cases. Aβ pathology is linked in humans to altered membrane protein and lipid composition, particularly involving lipid rafts. Although similar membrane alterations are unknown in non-human primates, membrane senescence is postulated to cause the activated β-amyloidogenic pathway, and Aβ pathology is the prevailing signature of non-human and human primate brain aging.
老年斑，主要是弥漫性的，以及脑淀粉样β（Aβ）血管病，在灵长类动物衰老大脑中很常见，从狐猴到非人类的人科动物。Aβ而不是过度磷酸化的 tau（HPtau）病变是非人类灵长类动物大脑衰老的常见命名蛋白病。衰老灵长类动物大脑中 Aβ的丰度可以很好地耐受，对认知功能的影响通常仅限于特定任务。相比之下，人类大脑衰老的特点是早期出现 HPtau 病变，主要形成神经纤维缠结、神经原纤维缠结的神经突、神经毡丝，Aβ沉积前几十年，其严重程度从脑干、内嗅皮层和海马体的某些核发展到边缘系统、新皮层和其他脑区。神经纤维缠结与晚期认知障碍和痴呆相关。在人类中，Aβ病变与膜蛋白和脂质组成的改变有关，特别是涉及脂筏。虽然在非人类灵长类动物中未知类似的膜改变，但推测膜衰老会导致激活的β-淀粉样生成途径，Aβ病变是非人类和人类灵长类动物大脑衰老的主要特征。
