ISSN 1214-0287 (on-line), ISSN 1214-021X (printed)
J Appl Biomed
Volume 8 (2010), No 3, p 121-130
DOI 10.2478/v10136-009-0015-7

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

Natividad de las Cuevas, Ursula Munoz, Fernando Bartolome, Noemi Esteras, Carolina Alquezar, Angeles Martin-Requero

Address: Angeles Martin-Requero, Centro de Investigaciones Biologicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain

Received 24th February 2010.
Revised 27th April 2010.
Published online 6th May 2010.

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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.

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

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