今天發(fā)表在BioMed Central開放期刊Journal of Neuroinflammation雜志上的一則研究表明，大腦慢性炎癥會引發(fā)阿爾茨海默氏癥。
迄今為止,，阿爾茨海默氏病（AD）與炎癥之間的相關關系一直得不到很好的闡述,，最近研究結果表明,，非甾體抗炎藥可以在疾病早期階段幫助AD患者，但想要得到確切的效益,，需長期治療,。
蘇黎世ETH與伯爾尼大學研究人員合作研究了什么樣的免疫系統(tǒng)會對AD小鼠疾病發(fā)展有影響。結果表明出生前存在感染的小鼠足以引發(fā)長期的老年神經系統(tǒng)變化以及顯著的記憶問題,。
這些老鼠炎性細胞因子水平的提高,，導致淀粉樣前體蛋白（APP）的水平增加，改變Tau蛋白的細胞定位,。這提示慢性炎癥可能是一個AD發(fā)展的早期事件,。（生物谷：Bioon.com）
doi:10.1186/1742-2094-9-151
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Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice
Dimitrije Krstic, Amrita Madhusudan, Jana Doehner, Prisca Vogel, Tina Notter, Claudine Imhof, Abigail Manalastas, Martina Hilfiker, Sandra Pfister, Cornelia Schwerdel, Carsten Riether, Urs Meyer and Irene Knuesel
Background
Alzheimer's disease (AD) is the most prevalent form of age-related dementia, and its effect on society increases exponentially as the population ages. Accumulating evidence suggests that neuroinflammation, mediated by the brain's innate immune system, contributes to AD neuropathology and exacerbates the course of the disease. However, there is no experimental evidence for a causal link between systemic infection or neuroinflammation and the onset of the disease.
Methods
The viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C) was used to stimulate the immune system of experimental animals. Wild-type (WT) and transgenic mice were exposed to this cytokine inducer prenatally (gestation day (GD)17) and/or in adulthood. Behavioral, immunological, immunohistochemical, and biochemical analyses of AD-associated neuropathologic changes were performed during aging.
Results
We found that a systemic immune challenge during late gestation predisposes WT mice to develop AD-like neuropathology during the course of aging. They display chronic elevation of inflammatory cytokines, an increase in the levels of hippocampal amyloid precursor protein (APP) and its proteolytic fragments, altered Tau phosphorylation, its mis-sorting to somatodendritic compartments, and significant impairments in working memory in old age. If this prenatal infection is followed by a second immune challenge in adulthood, the phenotype is strongly exacerbated, and mimics AD-like neuropathologic changes. These include deposition of APP and its proteolytic fragments, along with Tau aggregation, microglia activation and reactive gliosis. Whereas Abeta peptides were not significantly enriched in extracellular deposits of double immune-challenged WT mice at 15 months, they dramatically increased in age-matched immune-challenged transgenic AD mice, precisely around the inflammation-induced accumulations of APP and its proteolytic fragments, in striking similarity to the post-mortem findings in human patients with AD.
Conclusion
Chronic inflammatory conditions induce age-associated development of an AD-like phenotype in WT mice, including the induction of APP accumulations, which represent a seed for deposition of aggregation-prone peptides. The PolyI:C mouse model therefore provides a unique tool to investigate the molecular mechanisms underlying the earliest pathophysiological changes preceding fibrillary Abeta plaque deposition and neurofibrillary tangle formations in a physiological context of aging. Based on the similarity between the changes in immune-challenged mice and the development of AD in humans, we suggest that systemic infections represent a major risk factor for the development of AD.
