Rejuv Res：免疫系统可能缓解阿尔茨海默氏症

近日，科学家在小鼠动物研究发现免疫系统能去除β-淀粉样蛋白，β-淀粉样蛋白是大脑中引发阿尔茨海默氏症的致病物质。研究人员现在已经能证实免疫系统在人身上也有类似功效。

研究人员筛选700个血液样本中成千上万个基因的表达水平，结果发现免疫系统对抗β-淀粉样蛋白的标记物——CCR2基因。

研究小组使用一种常见的临床措施--精神状态检查量表法测量记忆和其他认知功能。

早期研究工作表明在小鼠体内CCR2激活血液中的免疫系统，结果能改善小鼠记忆，缓解阿尔茨海默氏症。

David Melzer教授说：研究结果非常令人兴奋，也许CCR2-相关免疫可以被用来减缓阿尔茨海默氏症，但需要开展更多研究工作以证明其安全和有效性。

doi:10.1089/rej.2011.1302
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Leukocyte CCR2 Expression Is Associated with Mini-Mental State Examination Score in Older Adults

Lorna W. Harries, Rachel M. Bradley-Smith, David J. Llewellyn, Luke C. Pilling, Alexander Fellows, William Henley, Dena Hernandez, Jack M. Guralnik, Stefania Bandinelli, Andrew Singleton, Luigi Ferrucci, and David Melzer.

Abstract

Introduction: Circulating inflammatory markers may play an important role in cognitive impairment at older ages. Mice deficient for the chemokine (C-C motif) receptor 2 (CCR2) develop an accelerated Alzheimer-like pathology. CCR2 is also important in neurogenesis. To identify human gene transcripts most closely associated with Mini-Mental State Examination (MMSE) scores, we undertook a genome-wide and inflammation specific transcriptome screen in circulating leukocytes from a population-based sample.

Methods: We measured in vivo transcript levels by microarray analysis in 691 subjects (mean age 72.6 years) in the InCHIANTI study (Invecchiare in Chianti, aging in the Chianti area). We assessed expression associations with MMSE performance at RNA collection and prior 9-year change in MMSE score in linear regression models.

Results: In genome-wide analysis, raised CCR2 expression was cross-sectionally the most strongly associated transcript with lower MMSE score (beta=−0.16, p=5.1×10⁻⁶, false discovery rate (FDR; q=0.077). Amongst inflammatory transcripts, only CCR2 expression was associated with both MMSE score and accelerated decline in score over the preceding 9 years (beta=−0.16, p=5.1×10⁻⁶, q=0.003; and beta=−0.13, p=5.5×10⁻⁵, q=0.03, respectively). CCR2 expression was also positively associated with apolipoprotein E (ApoE) e4 Alzheimer disease risk haplotype.

Conclusions: We show for the first time that CCR2 expression is associated with lower MMSE scores in an older human population. Laboratory models of Ccr2-mediated β-amyloid removal and regulation of neurogenesis affecting cognitive function may be applicable in humans. CCR2-mediated pathways may provide a possible focus for intervention to potentiate protective reactions to Alzheimer pathology in older people, including for people with an adverse ApoE haplotype.