Expression of calcipressin1, an inhibitor of the phosphatase calcineurin, is altered with aging and Alzheimer's disease.
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 Abeta 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.
Cook
Casey N
CN
Neuroscience Program, Loyola University Medical Center, 2160 S 1st Ave, Maywood, IL 60153, USA.
Hejna
Matthew J
MJ
Magnuson
Debra J
DJ
Lee
John M
JM
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002467:Cell Nucleus / Q000473:pathology; D004268:DNA-Binding Proteins; D004314:Down Syndrome / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000473:pathology; D012016:Reference Values; D013702:Temporal Lobe / Q000473:pathology; D015854:Up-Regulation; D016875:tau Proteins
D016229:Amyloid beta-Peptides; D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C108612:RCAN1 protein, human; D016875:tau Proteins