PDF(Pubmed)
Abstract：
Alzheimer disease (AD) is currently the leading cause of cognitive decline and dementia worldwide. Recently, studies have suggested that other neurodegenerative comorbidities such as limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), Lewy body disease (LBD), and cerebrovascular disease frequently co-occur with Alzheimer disease neuropathologic change (ADNC) and may have significant cognitive effects both in isolation and synergistically with ADNC. Herein, we study the relative clinical impact of these multiple neurodegenerative pathologies in 704 subjects. Each of these pathologies is relatively common in the cognitively impaired population, while cerebrovascular pathology and ADNC are the most common in cognitively normal individuals. Moreover, while the number of concurrent neuropathologic entities rises with age and has a progressively deleterious effect on cognition, 44.3% of cognitively intact individuals are resistant to having any neurodegenerative proteinopathy (compared to 15.2% of cognitively impaired individuals) and 83.5% are resistant to having multiple concurrent proteinopathies (compared to 64.6% of cognitively impaired individuals). The presence of at least 1 APOE ε4 allele was associated with impaired cognition and the presence of multiple proteinopathies, while APOE ε2 was protective against cumulative proteinopathies. These results indicate that maintenance of normal cognition may depend on resistance to the development of multiple concurrent proteinopathies.
摘要：
阿尔茨海默病(AD)是目前全球认知功能下降和痴呆的主要原因。最近,研究表明，其他神经退行性合并症，如边缘占优势的年龄相关的TDP-43脑病神经病理变化（LATE-NC），路易体病（LBD），和脑血管疾病经常与阿尔茨海默病神经病理变化（ADNC）同时发生，并且可能在单独和与ADNC协同作用下具有显着的认知作用。在这里，我们在704名受试者中研究了这些多发性神经退行性病变的相对临床影响.这些病症中的每一种在认知障碍人群中相对常见，而脑血管病理学和ADNC在认知正常个体中最常见。此外，虽然并发神经病理学实体的数量随着年龄的增长而增加，并对认知产生逐渐的有害影响，44.3％的认知完整个体对任何神经变性蛋白病有抵抗力（与15.2％的认知受损个体相比），83.5％对多种并发蛋白病有抵抗力（与64.6％的认知受损个体相比）。至少1个APOEε4等位基因的存在与认知功能受损和多种蛋白病的存在有关，而APOEε2对累积蛋白质病具有保护作用。这些结果表明，正常认知的维持可能取决于对多种并发蛋白质病发展的抵抗力。
