Display Settings:


Send to:

Choose Destination
Glia. 2010 Feb;58(3):300-14. doi: 10.1002/glia.20924.

Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease.

Author information

  • 1Department of Medical Science, Saitama Medical Center and University, Kawagoe, Saitama, Japan. t_mori@saitama-med.ac.jp


Alzheimer's disease (AD) is the most common progressive dementia and is pathologically characterized by brain deposition of amyloid-beta (Abeta) peptide as senile plaques. Inflammatory and immune response pathways are chronically activated in AD patient brains at low levels, and likely play a role in disease progression. Like microglia, activated astrocytes produce numerous acute-phase reactants and proinflammatory molecules in the AD brain. One such molecule, S100B, is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits. We have previously shown that augmented and prolonged activation of astrocytes has a detrimental impact on neuronal survival. Furthermore, we have implicated astrocyte-derived S100B as a candidate molecule responsible for this deleterious effect. To evaluate a putative relationship between S100B and AD pathogenesis, we crossed transgenic mice overexpressing human S100B (TghuS100B mice) with the Tg2576 mouse model of AD, and examined AD-like pathology. Brain parenchymal and cerebral vascular beta-amyloid deposits and Abeta levels were increased in bigenic Tg2576-huS100B mice. These effects were associated with increased cleavage of the beta-C-terminal fragment of amyloid precursor protein (APP), elevation of the N-terminal APP cleavage product (soluble APPbeta), and activation of beta-site APP cleaving enzyme 1. In addition, double transgenic mice showed augmented reactive astrocytosis and microgliosis, high levels of S100 expression, and increased levels of proinflammatory cytokines as early as 7-9 months of age. These results provide evidence that (over)-expression of S100B acts to accelerate AD-like pathology, and suggest that inhibiting astrocytic activation by blocking S100B biosynthesis may be a promising therapeutic strategy to delay AD progression..

(c) 2009 Wiley-Liss, Inc.

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (9)Free text

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Publication Types, MeSH Terms, Substances, Grant Support

PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for John Wiley & Sons, Inc. Icon for PubMed Central
    Loading ...
    Write to the Help Desk