Cerebral Small Vessel Disease in Sporadic and Familial Alzheimer Disease.
Cerebral Small Vessel Disease in Sporadic and Familial Alzheimer Disease.
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DOI：
10.1016/j.ajpath.2021.07.004
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Sepulveda-Falla D
中科院分区：
文献类型：
--
作者：
Kalaria RN;Sepulveda-Falla D
阿尔茨海默病（AD）是痴呆症最常见的原因。阿尔茨海默病的生物学定义仅限于β淀粉样蛋白斑块、神经原纤维病理和神经变性的大脑负担。然而，目前的证据表明，小血管疾病（SVD）的各种特征是散发性和家族性AD的一部分，并暗中改变了它们。神经影像学研究表明，由血管机制解释的白质高信号在AD谱系中经常发生。最近的研究进展进一步强调，家族性AD患者额叶脑室周围和后叶白质高信号与脑淀粉样血管病有关。尽管SVD标志物是否先于传统公认的疾病生物标志物尚存争议，但死后研究表明，SVD病理包括小皮质和皮质下梗死、微梗死、微出血、血管周围间隔和白质衰减，在散发性和突变携带者确诊的家族性AD中很常见。与年龄相关的脑血管病变，如小动脉硬化和脑淀粉样血管病，通过改变认知障碍和AD痴呆的阈值来改变进展或加重风险。在AD的生物学定义中，SVD作为生物标志物的结合是有必要的。直接减少脑淀粉样蛋白负担的治疗干预对疾病或延缓认知退化没有重大影响，但降低血管疾病的风险似乎是解决早发性和晚发性AD痴呆的唯一合理方法。
Alzheimer disease (AD) is the most common cause of dementia. Biological definitions of AD are limited to the cerebral burden of amyloid β plaques, neurofibrillary pathology, and neurodegeneration. However, current evidence suggests that various features of small vessel disease (SVD) are part of and covertly modify both sporadic and familial AD. Neuroimaging studies suggest that white matter hyperintensities explained by vascular mechanisms occurs frequently in the AD spectrum. Recent advances have further emphasized that frontal periventricular and posterior white matter hyperintensities are associated with cerebral amyloid angiopathy in familial AD. Although whether SVD markers precede the classically recognized biomarkers of disease is debatable, post-mortem studies show that SVD pathology incorporating small cortical and subcortical infarcts, microinfarcts, microbleeds, perivascular spacing, and white matter attenuation is commonly found in sporadic as well as in mutation carriers with confirmed familial AD. Age-related cerebral vessel pathologies such as arteriolosclerosis and cerebral amyloid angiopathy modify progression or worsen risk by shifting the threshold for cognitive impairment and AD dementia. The incorporation of SVD as a biomarker is warranted in the biological definition of AD. Therapeutic interventions directly reducing the burden of brain amyloid β have had no major impact on the disease or delaying cognitive deterioration, but lowering the risk of vascular disease seems the only rational approach to tackle both early- and late-onset AD dementia.
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影响因子：
8.8
作者：
Arber C;Lovejoy C;Harris L;Willumsen N;Alatza A;Casey JM;Lines G;Kerins C;Mueller AK;Zetterberg H;Hardy J;Ryan NS;Fox NC;Lashley T;Wray S
通讯作者：
Wray S
DOI：
10.1111/bpa.12888
发表时间：
2020-11
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
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DOI：
10.1002/dad2.12053
发表时间：
2020-01-01
影响因子：
5.3
作者：
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影响因子：
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作者：
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