Affiliations: [a] Neuroscience Program, Loyola University Medical Center, 2160 S 1st Ave, Maywood, IL 60153, USA | [b] Departments of Pathology and Pharmacology, Loyola University Medical Center, 2160 S 1st Ave, Maywood, IL 60153, USA
Correspondence:
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Corresponding author: John M. Lee M.D. Ph.D., Loyola University Medical Center, Department of Pathology, 2160 S 1st Ave, Bldg 102, Rm 2638, Maywood, IL 60153, USA. Tel.: +1 708 216 4774; Fax: +1 708 216 6735; E-mail: Jlee2@lumc.edu.
Abstract: Protein phosphatase 2B (calcineurin) activity has been shown to be decreased in Alzheimer's disease and is a possible mechanism(s) for the hyperphosphorylation of tau and subsequent neurofibrillary tangle formation. Recently, mRNA expression of Down's syndrome Critical Region 1 gene, which encodes the protein calcipressin (an endogenous inhibitor of calcineurin), was found to be upregulated in both Down's syndrome and Alzheimer's disease. Calcipressin is induced by oxidative stress and Aβ in vitro, further establishing a link in the pathology of both diseases. Using immunohistochemistry techniques, calcipressin protein expression in the pyramidal neurons of the temporal lobe was shown to increase with aging (r2=0.5658; p=0.0313), and also in moderate to severe Alzheimer's disease compared to control patients (t=3.872; p=0.0017). In addition, there was a positive correlation between the total number of calcipressin-positive pyramidal neurons and the number of neurofibrillary tangles in the temporal cortex (r2= 0.5955; p=0.0249). As there was an 88% increase in nuclear calcipressin in Alzheimer's disease (p=0.0001), the relationship between cellular localization of calcipressin and neurofibrillary tangle formation was investigated, which revealed a decrease in neurofibrillary tangle-bearing neurons that contain nuclear calcipressin (t=4.874; p=0.0028) and further demonstrates that the cellular regulation of calcipressin is altered in Alzheimer's disease.
