Seeding plaques in Alzheimer's disease.
Seeding plaques in Alzheimer's disease.
复制标题
在阿尔茨海默病中播种斑块。
DOI：
10.1111/j.1471-4159.2011.07574.x
复制
发表时间：
2012
影响因子：
4.7
通讯作者：
Baron,Gerald
中科院分区：
文献类型：
--
作者：
Prado,MarcoAM;Baron,Gerald
The increasing burden of Alzheimer’s disease (AD), due to aging of the world’s population, has led many scientists and policy makers to suggest that AD will become one of the major causes of economic and health distress in the next few decades. Alzheimer’s disease predominantly affects episodic memory causing impaired cognitive function and eventually a loss of one’s identity. The pathological hallmarks of AD are extracellular plaques, formed by aggregation of amyloid-β peptides (Aβ) and other proteins, as well as intracellular neurofibrillary tangles, due to Tau hyperphosphorylation. In addition to these pathological hallmarks, several lines of evidence indicate that soluble oligomeric forms of Aβ-peptides are likely to be one of the early toxic components in the disease. Albeit still under debate, many researchers accept the notion that increased levels of distinct forms of Aβ oligomers trigger a cascade of pathological changes that culminates with cognitive deficits and ultimately to neuronal death (Ono and Yamada 2011).There are many aspects of the role of Aβ peptides in Alzheimer’s disease that remain poorly understood. One subject on which we still have scarce knowledge is the relationship between distinct species of Aβ oligomers and generation of amyloid plaques. Remarkably, synaptic activity seems to directly regulate the amount Aβ peptides released into the interstitial fluid; long-term changes in neuronal activity can alter the levels of extracellular Aβ and influence plaque deposition (Bero et al. 2011). These results agree with the proposal that a default mode network in the brain, defined by its functional connectivity during resting state, may be a key player in the cognitive and pathological dysfunction found in AD (Sperling et al. 2009). Indeed, the notion that Aβ deposits may be related to the level of endogenous neuronal connectivity in the resting state is enticing. Importantly, plaques are dynamic entities able to both capture aggregated forms of Aβ as well as to free some previously captured soluble oligomers (Selkoe 2011). Unfortunately, little is known about the equilibrium dynamics of Aβ deposits and its soluble forms.
