Tau and TDP-43 synergy: a novel therapeutic target for sporadic late-onset Alzheimer's disease.
Tau and TDP-43 synergy: a novel therapeutic target for sporadic late-onset Alzheimer's disease.
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DOI：
10.1007/s11357-021-00407-0
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发表时间：
2021-08
期刊：
影响因子：
5.6
通讯作者：
Liachko NF
中科院分区：
文献类型：
--
作者：
Latimer CS;Liachko NF
阿尔茨海默病(AD)的传统定义是大脑中存在两种类型的蛋白质聚集体：由淀粉样蛋白β(Aβ)组成的淀粉样斑块和含有tau蛋白的神经原纤维缠结。然而，很大比例(高达57%)的AD患者也有TDP-43聚集体，作为另一种共病病理。TDP-43聚集体在AD中的存在与海马区硬化、更严重的脑萎缩、更严重的认知损害和更快的认知衰退相关。在患有β、tau和tdp-43混合病理的患者中，tdp-43可能与AD的神经退行性变过程相互作用，从而恶化预后。虽然在AD和迟发性痴呆的TDP-43病理特征方面已经取得了相当大的进展，但仍然迫切需要机制研究来了解潜在的疾病生物学和开发治疗干预措施。本文综述了尸检队列研究和基于模型生物体的研究对这些过程的理解，并建议将tau和TDP-43之间的神经毒性协同作用作为治疗合并TDP-43病理的AD的一种新的治疗策略。
Alzheimer’s disease (AD) is traditionally defined by the presence of two types of protein aggregates in the brain: amyloid plaques comprised of the protein amyloid-β (Aβ) and neurofibrillary tangles containing the protein tau. However, a large proportion (up to 57%) of AD patients also have TDP-43 aggregates present as an additional comorbid pathology. The presence of TDP-43 aggregates in AD correlates with hippocampal sclerosis, worse brain atrophy, more severe cognitive impairment, and more rapid cognitive decline. In patients with mixed Aβ, tau, and TDP-43 pathology, TDP-43 may interact with neurodegenerative processes in AD, worsening outcomes. While considerable progress has been made to characterize TDP-43 pathology in AD and late-onset dementia, there remains a critical need for mechanistic studies to understand underlying disease biology and develop therapeutic interventions. This perspectives article reviews the current understanding of these processes from autopsy cohort studies and model organism-based research, and proposes targeting neurotoxic synergies between tau and TDP-43 as a new therapeutic strategy for AD with comorbid TDP-43 pathology.
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影响因子：
5.6
作者：
Deshimaru M;Kinoshita-Kawada M;Kubota K;Watanabe T;Tanaka Y;Hirano S;Ishidate F;Hiramoto M;Ishikawa M;Uehara Y;Okano H;Hirose S;Fujioka S;Iwasaki K;Yuasa-Kawada J;Mishima T;Tsuboi Y
通讯作者：
Tsuboi Y
影响因子：
4.2
作者：
Chan, Dennis;Shafto, Meredith;Henson, Rik N.
通讯作者：
Henson, Rik N.
影响因子：
8.8
作者：
Hsieh, Yi-Chen;Guo, Caiwei;Shulman, Joshua M.
通讯作者：
Shulman, Joshua M.
DOI：
10.1093/geronb/gbw124
发表时间：
2017-01
期刊：
The journals of gerontology. Series B, Psychological sciences and social sciences
影响因子：
--
作者：
Gow AJ;Pattie A;Deary IJ
通讯作者：
Deary IJ
影响因子：
12.7
作者：
Josephs KA;Murray ME;Whitwell JL;Tosakulwong N;Weigand SD;Petrucelli L;Liesinger AM;Petersen RC;Parisi JE;Dickson DW
通讯作者：
Dickson DW