Calmodulin levels in blood cells as a potential biomarker of Alzheimer’s disease

Abstract

IntroductionThe clinical features of Alzheimer’s disease (AD) overlap with a number of other dementias and conclusive diagnosis is only achieved at autopsy. Accurate in-life diagnosis requires finding biomarkers suitable for early diagnosis, as well as for discrimination from other types of dementia. Mounting evidence suggests that AD-dependent processes may also affect peripheral cells. We previously reported that calmodulin (CaM) signaling is impaired in AD lymphoblasts. Here, we address the issue as to whether the assessment of CaM levels in peripheral cells could serve as a diagnostic biomarker.MethodsA total of 165 subjects were enrolled in the study, including 56 AD patients, 15 patients with mild cognitive impairment, 7 with frontotemporal dementia associated with progranulin mutations, 4 with dementia with Lewy bodies, 20 patients with Parkinson’s disease, 10 with amyotrophic lateral sclerosis, 5 with progressive supranuclear palsy, and 48 cognitively normal individuals. CaM levels were then analyzed in lymphoblasts, peripheral blood mononuclear cells and plasma. Receiver operating characteristic (ROC) curve analyses were employed to evaluate the diagnostic performance of CaM content in identifying AD patients.ResultsCompared with control individuals, CaM levels were significantly increased in AD cells, but not in the other neurodegenerative disorders. CaM levels differentiated AD from control with a sensitivity of 0.89 and a specificity of 0.82 and were not dependent on disease severity or age. MCI patients also showed higher levels of the protein.ConclusionsCaM levels could be considered a peripheral biomarker for AD in its early stage and help to discriminate from other types of dementia.

Progranulin deficiency induces overactivation of WNT5A expression via TNF-α/NF-κB pathway in peripheral cells from frontotemporal dementia-linked granulin mutation carriers

“…46,[52][53][54] For this reason, peripheral cells, such as fibroblasts or blood lymphocytes, have been used extensively in the search for useful biomarkers that may correlate with expression and/or progression of disease. [55][56][57][58] In this regard, it has been shown that peripheral cells from patients with neurodegenerative disorders display cell cycle disturbances, 45,[59][60][61][62] reflecting the unscheduled cell cycle re-entry of postmitotic neurons and leading to apoptotic cell death. [63][64][65] The present work was undertaken to elucidate possible mechanisms involved in the PGRN deficiencyinduced WNT5A expression and signalling in PGRNdeficient lymphoblasts from patients with FTLD-TDP that were considered responsible for the increased activation of the CDK6/pRb-mediated cell proliferation.…”

Characterization and expression analysis of Calmodulin (CaM) in orange-spotted grouper (Epinephelus coioides) in response to Vibrio alginolyticus challenge

“…These results suggested that Ec-CaM transcript expression showed a significant increase following the vibrio challenge, which may respond to the bacterial stimulation and neutralize the adverse effects of the vibrio invasion. In mammal, CaM signaling is impaired in lymphoblast of Alzheimer's disease, thus CaM level in blood cells can be regarded as a potential biomarker of Alzheimer's disease (Esteras et al 2013). Recent studies indicate that CaM is also considered as one of the most promising molecular indicators in teleost exposed to the chronic stressors (Alves et al 2010).…”

Interleukin-11: A Multifunctional Cytokine with Intrinsically Disordered Regions

“…The affinities of S100B and calmodulin to IL-11 [(6.1 ± 1.6) 9 10 -6 M and (1.9 ± 0.3) 9 10 -5 M, respectively] are insufficient for their interaction with IL-11 in blood, since plasma concentrations of S100B, calmodulin, and IL-11 are within dozens of picomoles [39,53,54]. Meanwhile, high intracellular concentrations of calmodulin and S100B (up to dozens of micromoles [55,56]), NCS-1 (micromoles in the nervous system [57]), Cell Biochem Biophys and GCAP-1/2 (micromoles [58]) open up the possibility of their local interaction with extracellular IL-11 in processes accompanied by the disintegration of plasma membrane and efflux of cellular contents into the extracellular space.…”