人們已知道,，老年癡呆癥與異常纖維蛋白沉積物在患者腦部堆積有關(guān),。如果能清除這些腦中的“垃圾”,，就有望改善病狀。德國一項(xiàng)新研究顯示,，人體自身免疫系統(tǒng)產(chǎn)生的一些特殊巨噬細(xì)胞能在這方面發(fā)揮“清潔工”的作用,。
德國柏林沙里泰大學(xué)醫(yī)院和弗賴堡大學(xué)醫(yī)院的研究人員在新一期美國《神經(jīng)科學(xué)期刊》上報(bào)告說,，他們經(jīng)過10年動(dòng)物研究發(fā)現(xiàn)，骨髓中產(chǎn)生的一些特殊巨噬細(xì)胞可以降解和清除引起老年癡呆癥的有害沉積物,。
研究人員還首次發(fā)現(xiàn)一種特殊的趨化因子，可以發(fā)號(hào)施令讓巨噬細(xì)胞進(jìn)行專業(yè)分工,，并運(yùn)動(dòng)到腦中執(zhí)行“清潔”任務(wù),。研究人員認(rèn)為，這一發(fā)現(xiàn)為治療老年癡呆癥提供了一個(gè)全新思路,。他們相信將來可以由此開發(fā)出一種定位準(zhǔn)確且副作用小的老年癡呆癥新療法。(生物谷 Bioon.com)
doi:10.1523/?JNEUROSCI.6209-10.2011
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Distinct and Non-Redundant Roles of Microglia and Myeloid Subsets in Mouse Models of Alzheimer's Disease
Distinct and Non-Redundant Roles of Microglia and Myeloid Subsets in Mouse Models of Alzheimer's Disease
Mononuclear phagocytes are important modulators of Alzheimer's disease (AD), but the specific functions of resident microglia, bone marrow-derived mononuclear cells, and perivascular macrophages have not been resolved. To elucidate the spatiotemporal roles of mononuclear phagocytes during disease, we targeted myeloid cell subsets from different compartments and examined disease pathogenesis in three different mouse models of AD (APPswe/PS1, APPswe, and APP23 mice). We identified chemokine receptor 2 (CCR2)-expressing myeloid cells as the population that was preferentially recruited to β-amyloid (Aβ) deposits. Unexpectedly, AD brains with dysfunctional microglia and devoid of parenchymal bone marrow-derived phagocytes did not show overt changes in plaque pathology and Aβ load. In contrast, restriction of CCR2 deficiency to perivascular myeloid cells drastically impaired β-amyloid clearance and amplified vascular Aβ deposition, while parenchymal plaque deposition remained unaffected. Together, our data advocate selective functions of CCR2-expressing myeloid subsets, which could be targeted specifically to modify disease burden in AD.
