It's of interest that mRNA levels of the calcineurin inhibitor, DSCR1, are also much higher in AD brain (1). The recent study be Lee and colleagues finds that DSCR1 interacts with Tollip and positively modulates IL-1R signalling (2). Tollip is an IRAK-1 inhibitor. This would seem to suggest problems with TLR2/TLR4 signalling in AD. This is supported by the Landreth study finding that CD14 and TLR2 and TLR4 bind Aβ to stimulate microglial activation (3). The KEGG link is below for the TOLL RECEPTOR signaling pathway (4).

References:
1. Ermak G, Morgan TE, Davies KJ. Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer's disease. J Biol Chem. 2001 Oct 19;276(42):38787-94. Abstract

2. Lee JY, Lee HJ, Lee EJ, Jang SH, Kim H, Yoon JH, Chung KC. Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling. Biochim Biophys Acta. 2009 Dec;1790(12):1673-80. Abstract

3. Reed-Geaghan EG, Savage JC, Hise AG, Landreth GE. CD14 and toll-like receptors 2 and 4 are required for fibrillar A{beta}-stimulated microglial activation. J Neurosci. 2009 Sep 23;29(38):11982-92. Abstract

4. Toll-like receptor signaling pathway—Homo sapiens (human)

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