Department of Neurology, The University of Texas Health Science Center at Houston, 6431 Fannin, St. Houston, TX, 77030, USA.
Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibanez, Santiago, Chile.
Acta Neuropathol Commun. 2021 Mar 30;9(1):56. doi: 10.1186/s40478-021-01155-0.
Amyloid-β (Aβ) misfolding is one of the hallmark pathological features of Alzheimer's disease (AD). AD can manifest with diverse symptomatology including variable rates of cognitive decline, duration of clinical disease, and other detrimental changes. Several reports suggest that conformational diversity in misfolded Aβ is a leading factor for clinical variability in AD, analogous to what it has been described for prion strains in prion diseases. Notably, prion strains generate diverse patterns of misfolded protein deposition in the brains of affected individuals. Here, we tested the in vivo prion-like transmission features of four AD brains displaying particular patterns of amyloidosis. AD brains induced different phenotypes in recipient mice, as evaluated by their specific seeding activity, as well as the total amount of Aβ deposited surrounding vascular structures and the reactivity of amyloid pathology to thioflavin S. Our results support the notion that AD-subtypes are encoded in disease-associated Aβ. Further research exploring whether AD include a spectrum of different clinical conditions or syndromes may pave the way to personalized diagnosis and treatments.
淀粉样蛋白-β（Aβ）错误折叠是阿尔茨海默病（AD）的标志性病理特征之一。AD 可表现出多种症状，包括认知能力下降的速度不同、临床疾病的持续时间和其他有害变化。有几项报告表明，错误折叠的 Aβ的构象多样性是 AD 临床变异性的主要因素，类似于在朊病毒疾病中描述的朊病毒株。值得注意的是，朊病毒株会在受影响个体的大脑中产生不同模式的错误折叠蛋白沉积。在这里，我们测试了四个表现出特定淀粉样变性模式的 AD 大脑的体内类朊病毒样传播特征。AD 大脑通过其特定的接种活性以及在血管结构周围沉积的 Aβ总量以及淀粉样蛋白病理对硫黄素 S 的反应性，在受者小鼠中诱导了不同的表型。我们的结果支持这样一种观点，即 AD 亚型是由与疾病相关的 Aβ编码的。进一步探索 AD 是否包含一系列不同的临床病症或综合征的研究可能为个性化诊断和治疗铺平道路。
