人们已知道,老年痴呆症与异常纤维蛋白沉积物在患者脑部堆积有关。如果能清除这些脑中的“垃圾”,就有望改善病状。德国一项新研究显示,人体自身免疫系统产生的一些特殊巨噬细胞能在这方面发挥“清洁工”的作用。
德国柏林沙里泰大学医院和弗赖堡大学医院的研究人员在新一期美国《神经科学期刊》上报告说,他们经过10年动物研究发现,骨髓中产生的一些特殊巨噬细胞可以降解和清除引起老年痴呆症的有害沉积物。
研究人员还首次发现一种特殊的趋化因子,可以发号施令让巨噬细胞进行专业分工,并运动到脑中执行“清洁”任务。研究人员认为,这一发现为治疗老年痴呆症提供了一个全新思路。他们相信将来可以由此开发出一种定位准确且副作用小的老年痴呆症新疗法。(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.