■唐氏综合症(DS)是最常见的染色体疾病之一。大多数患有DS的个体在50岁时发展为阿尔茨海默病(AD)。最近的证据表明,蓝斑(LC)中的AD病理是散发性AD的早期事件。LC神经元的广泛轴突网络可能有助于AD大脑中tau病理学的传播,尽管尚未在DS-AD中进行调查。
■这项研究的主要目的是描述LC中的AD病理和神经炎症,比较死后人体组织中的AD和DS-AD。
■我们利用了pTau(4种不同形式)的免疫荧光和半定量分析,淀粉样蛋白-β(Aβ),胶质,和36例LC中的神经元标志物(对照,DS-AD,和AD)以比较不同的病理概况。
■与LOAD或EOAD病例相比,DS-AD病例中的低聚tau高度升高。与LOAD组相比,pT231的染色分布在DS-AD和EOAD中升高。与AD病例相比,DS-AD组的Aβ免疫染色增加。与LOAD病例相比,在EOAD和DS-AD病例之间携带tau的神经元的数量也显著不同。
■虽然发炎,pTau,Aβ和Aβ都与AD病理有关,它们对疾病进展的贡献可能因诊断而异.我们的结果表明,DS-AD和EOAD在病理学上可能比LOAD更相似。我们的研究强调了独特的途径,以进一步理解AD神经病理学的机制。
UNASSIGNED: Down syndrome (DS) is one of the most commonly occurring chromosomal conditions. Most individuals with DS develop Alzheimer\'s disease (AD) by 50 years of age. Recent evidence suggests that AD pathology in the locus coeruleus (LC) is an early event in sporadic AD. It is likely that the widespread axonal network of LC neurons contributes to the spread of tau pathology in the AD brain, although this has not been investigated in DS-AD.
UNASSIGNED: The main purpose of this study was to profile AD pathology and neuroinflammation in the LC, comparing AD and DS-AD in postmortem human tissues.
UNASSIGNED: We utilized immunofluorescence and semi-quantitative analyses of pTau (4 different forms), amyloid-β (Aβ), glial, and neuronal markers in the LC across 36 cases (control, DS-AD, and AD) to compare the different pathological profiles.
UNASSIGNED: Oligomeric tau was highly elevated in DS-AD cases compared to LOAD or EOAD cases. The distribution of staining for pT231 was elevated in DS-AD and EOAD compared to the LOAD group. The DS-AD group exhibited increased Aβ immunostaining compared to AD cases. The number of tau-bearing neurons was also significantly different between the EOAD and DS-AD cases compared to the LOAD cases.
UNASSIGNED: While inflammation, pTau, and Aβ are all involved in AD pathology, their contribution to disease progression may differ depending on the diagnosis. Our results suggest that DS-AD and EOAD may be more similar in pathology than LOAD. Our study highlights unique avenues to further our understanding of the mechanisms governing AD neuropathology.