SUMMARY
The most common cause of dementia in the elderly is Alzheimer disease (AD). In Europe, AD is a leading cause of death. The prevalence of this disease in developed countries is increasing because of very significant shifts in life expectancy and demographic parameters. AD is characterized by progressive cognitive impairment, resulting from dysfunction and degeneration of neurons in the limbic and cortical regions of the brain. Two prominent abnormalities in the affected brain regions are extracellular deposits of beta-amyloid, and intracellular aggregates of tau protein in neurofibrillary tangles. The role of these features in AD pathogenesis and progression is not yet completely elucidated. Research over the last decade has revealed that the activation of cell cycle machinery in postmitotic neurons is one of the earliest events in neuronal degeneration in AD. Here we summarize evidence to support the hypothesis that cell cycle alterations occur in cells other than neurons in AD sufferers. Immortalized lymphocytes from AD patients have show an enhanced rate of proliferation associated with G1/S regulatory failure induced by alterations in the cyclin/CDK/pRb/E2F pathway. In addition, these cells have a higher resistance to serum deprivation-induced apoptosis. These neoplastic-like features, cell cycle dysfunction and impaired apoptosis can be considered systemic manifestations of AD disease.
KEY WORDS
Alzheimer's disease; lymphocytes; cell cycle; cell survival; p27; p21; calmodulin; PI3K/Akt; ERK1/2
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CITED
Esteras N, Alquezar C, Bermejo-Pareja F, Bialopiotrowicz E, Wojda U, Martin-Requero A. Downregulation of extracellular signal-regulated kinase 1/2 activity by calmodulin KII modulates p21(Cip1) levels and survival of immortalized lymphocytes from Alzheimer's disease patients. Neurobiol Aging. 34: 1090-1100, 2013.
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