Tau and neuroinflammation: What impact for Alzheimer's Disease and Tauopathies?

被引:267
作者
Laurent, Cyril [1 ,2 ,3 ]
Buee, Luc [1 ,2 ,3 ]
Blum, David [1 ,2 ,3 ]
机构
[1] Univ Lille, Lille, France
[2] INSERM, UMR S1172, Alzheiumer & Tauopathies, Lille, France
[3] Labex DISTALZ, Lille, France
关键词
Alzheimer's disease; Tau; Inflammation; Glia; Astrocytes; Microglia; PROGRESSIVE SUPRANUCLEAR PALSY; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; HIPPOCAMPAL SYNAPTIC-TRANSMISSION; GENOME-WIDE ASSOCIATION; TRANSGENIC MOUSE MODEL; IN-VIVO; MICROGLIAL ACTIVATION; AMYLOID-BETA; T-CELLS;
D O I
10.1016/j.bj.2018.01.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimer's Disease (AD) is a chronic neurodegenerative disorder and the most common type of dementia (60-80% of cases). In 2016, nearly 44 million people were affected by AD or related dementia. AD is characterized by progressive neuronal damages leading to subtle and latter obvious decline in cognitive functions including symptoms such as memory loss or confusion, which ultimately require full-time medical care. Its neuropathology is defined by the extracellular accumulation of amyloid-beta (A beta) peptide into amyloid plaques, and intraneuronal neurofibrillary tangles (NFT) consisting of aggregated hyper- and abnormal phosphorylation of tau protein. The latter, identified also as Tau pathology, is observed in a broad spectrum of neurological diseases commonly referred to as "Tauopathies". Besides these lesions, sustained neuroinflammatory processes occur, involving notably micro- and astro-glial activation, which contribute to disease progression. Recent findings from genome wide association studies further support an instrumental role of neuroinflammation. While the interconnections existing between this innate immune response and the amyloid pathogenesis are widely characterized and described as complex, elaborated and evolving, only few studies focused on Tau pathology. An adaptive immune response takes place conjointly during the disease course, as indicated by the presence of vascular and parenchymal T-cell in AD patients' brain. The underlying mechanisms of this infiltration and its consequences with regards to Tau pathology remain understudied so far. In the present review, we highlight the interplays existing between Tau pathology and the innate/adaptive immune responses.
引用
收藏
页码:21 / 33
页数:13
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