alexa Differential regulation of toll-like receptor mRNAs in amyloid plaque-associated brain tissue of aged APP23 transgenic mice.


Journal of Alzheimers Disease & Parkinsonism

Author(s): Frank S, Copanaki E, Burbach GJ, Mller UC, Deller T

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Abstract Alzheimer's disease (AD) is characterized by the pathological deposition of amyloid-beta protein in the aged brain. Inefficient clearance of amyloid-beta from brain tissue is believed to play a major role in the pathogenesis of these deposits. Since amyloid-beta clearance likely involves activation of microglial cells via toll-like receptors and since these receptors and their signaling pathways are regarded as potential therapeutic targets, we have studied the expression of toll-like receptor (tlr) mRNAs in an animal model of AD (APP23 transgenic mice). Laser microdissection was used to harvest plaques, tissue surrounding plaques and plaque-free tissue from cortex of aged APP23 transgenic mice and age-matched controls. Real-time RT-PCR was employed to quantify expression levels of different tlr mRNAs in these tissues. This revealed a strong upregulation of tlr2, tlr4, tlr5, tlr7 and tlr9 mRNAs in plaque material compared to plaque-free tissue. In contrast, tlr3 was not significantly upregulated. Plaque-free tissue did not show an increased expression of any tlr mRNAs compared to age-matched control mice. Double-immunofluorescence for TLR2 and the microglial marker Iba1 was used to demonstrate localization of TLR2 on plaque-associated microglia. Taken together, these data show a strong upregulation of mRNAs encoding surface TLRs in plaque-associated brain tissue of aged APP23 transgenic mice. Since TLR-upregulation is restricted to plaques, modifying TLR-signaling may be a promising therapeutic strategy for plaque removal. This article was published in Neurosci Lett and referenced in Journal of Alzheimers Disease & Parkinsonism

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