. Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy. Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1261-6. PubMed.


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  1. This interesting paper by Hawkes and McLaurin provides additional evidence that blood-borne macrophages are competent Aβ phagocytes. Their work further cements concepts from previous reports, which showed that blood-derived monocytes exist near cerebral vessels and β amyloid plaques (Stalder et al., 2005), and that genetic ablation of these cells increases parenchymal β amyloid load in mouse models of AD (Simard et al., 2006; El Khoury et al., 2007). Further, we have recently shown that genetic interruption of transforming growth factor-β signaling in innate immune cells results in accumulation of macrophages in cerebral vessels, brain penetration of these cells, and their clearance of both cerebral vascular and parenchymal β amyloid deposits in AD model mice (Town et al., 2008).

    Hawkes and McLaurin specifically draw attention to the perivascular macrophage subset. They have performed two definitive in-vivo experiments to discern the functional role of these cells in the context of AD-like pathology in TgCRND8 mice: 1) they reduced numbers of perivascular macrophages using clodronate, and 2) increased turnover of these cells using chitin. Results from both experiments suggest that perivascular macrophages are an important class of Aβ phagocytes that serve to limit cerebral amyloid angiopathy. Interestingly, these cells were unable to migrate into the brain parenchyma, and instead were restricted to cerebral vessels. It will be important to further discern the signals necessary to promote both brain penetration of these cells and Aβ engulfment/clearance in the AD brain. Elucidation of these signals will likely lead to novel therapeutic targets for the human syndrome.


    . Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med. 2007 Apr;13(4):432-8. PubMed.

    . Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron. 2006 Feb 16;49(4):489-502. PubMed.

    . Invasion of hematopoietic cells into the brain of amyloid precursor protein transgenic mice. J Neurosci. 2005 Nov 30;25(48):11125-32. PubMed.

    . Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat Med. 2008 Jun;14(6):681-7. PubMed.

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