J Appl Biomed 8:121-130, 2010 | DOI: 10.2478/v10136-009-0015-7

Cell cycle and Alzheimer's disease: studies in non-neuronal cells

Natividad de las Cuevas1, Úrsula Muñoz1, Fernando Bartolomé1, Noemí Esteras1, Carolina Alquezar1, Ángeles Martín-Requero1,2,*
1 Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain
2 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain

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 β-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.

Keywords: Alzheimer's disease; lymphocytes; cell cycle; cell survival; p27; p21; calmodulin; PI3K, Akt; ERK1, 2

Received: February 24, 2010; Revised: April 27, 2010; Published: July 31, 2010  Show citation

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de las Cuevas N, Muñoz Ú, Bartolomé F, Esteras N, Alquezar C, Martín-Requero Á. Cell cycle and Alzheimer's disease: studies in non-neuronal cells. J Appl Biomed. 2010;8(3):121-130. doi: 10.2478/v10136-009-0015-7.
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