Calcineurin (phosphatase 2B) is Present in Neurons Containing Neurofibrillary Tangles and in a Subset of Senile Plaques in Alzheimer's Disease

Fine Mapping of Calcineurin (PPP3CA) Gene Reveals Novel Alternative Splicing Patterns, Association of 5′UTR Trinucleotide Repeat With Addiction Vulnerability, and Differential Isoform Expression in Alzheimer's Disease

“…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.…”

A Role for Calcineurin in Alzheimers Disease

“…CaN was one of the phosphatases demonstrated to dephosphorylate tau, in vitro [14-15, 87]. At the same time, two independent groups reported that tangle-containing neurons and neurons surrounding plaques in AD brain showed strong CaN immunoreactivity [88, 89]; promoting the hypothesis that CaN modulated tau phosphorylation and suggested that decreased CaN activity may be in part responsible for hyperphosphorylation of tau [87]. Calcipressin, an endogenous CaN inhibitor, is found at high levels in AD brain, seemingly supporting the hypothesis that CaN phosphatase activity is decreased [90, 91].…”

Selective induction of calcineurin activity and signaling by oligomeric amyloid beta

“…Increased CaN activity has been found in the CNS of aging rats where it correlates with the degree of age-related cognitive impairments (Foster et al, 2001). Alteration of CaN has also been demonstrated in the AD brain (Brion et al, 1995; Hata et al, 2001; Norris et al, 2005) and in APP transgenic mice where Aβ-promoted neurite degeneration in the CNS is triggered by a Ca 2+ /CaN-dependent mechanism (Kuchibhotla et al, 2008). Furthermore, in vitro evidence indicates that Aβ induces neuronal apoptosis through a CaN-dependent mechanism (Agostinho and Oliveira, 2003).…”