Calcineurin upregulation has been postulated in AD brain due to its involvement in calcium homeostasis (Liu et al., 2005a,b) and inflammatory responses AD (Norris et al., 2005), whereas calcineurin downregulation has been postulated based on oxidative stress (Celsi et al., 2007), pathological cell losses and/or other pathological cellular damage (Brion, Couck, & Conreur, 1995). Alterations in phosphoregulation do provide major pathways by which cytoskeleton proteins, especially tau, (Lian, Ladner, Magnuson, & Lee, 2001) contribute to the neurofibrillary pathology characteristic of AD. Our observations that majority of PPP3CA isoform expression is reduced in AD postmortem brains thus supports much, though not all, prior work. Evidence for the specificity of this observation also comes from the study of expression of specific isoforms. Identification of the isoform that excludes exon 14 and is expressed at levels that are higher in AD than in control samples is of special interest, despite the fact that the function of the amino acids deleted in this isoform has not been well documented. Conceivably, the alternative splicing factors that produce CNEX13-14 and 13-15 might be altered in AD
