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Int J Clin Exp Pathol 2(4),390-398;2009

Original Article
Distinct Regulation of Cell Cycle and Survival in Lymphocytes from Patients with
Alzheimer’s Disease and Amyotrophic Lateral Sclerosis

Fernando Bartolomé, Úrsula Muñoz, Noemí Esteras, Jesús Esteban, Félix Bermejo-Pareja and Ángeles Martín-Requero

Department of Cellular and Molecular Pathophysiology. Centro de Investigaciones Biológicas (CSIC), Hospital Doce de Octubre, Centro de
Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Centro de Investigación Biomédica en Red de
Enfermedades Raras (CIBERER), Ramiro de Maéztu 9, 28040 Madrid, Spain

Received 14 November 2008; Accepted 25 November 2008; Available online 01 December 2008

Abstract: Alterations in cell cycle progression seem to be associated with neuronal death in Alzheimer’s disease (AD) and Amyotrophic Lateral
Sclerosis (ALS). We previously reported disturbances in the control of cell survival/death fate in immortalized lymphocytes from AD patients.
These cell cycle dysfunction and impaired apoptosis were considered systemic manifestations of AD disease. The purpose of this study was
to evaluate whether these abnormalities might turn out be typical of AD, or they are common to other neurodegenerative disorder such ALS. Our
results indicate that alterations in signaling molecules, Akt and ERK1/2, and in the cyclin-dependent kinase complex inhibitors (CDKis)
p21Cip1 and p27Kip1 are detectable in lymphoblasts from AD patients, but not in ALS patients, suggesting that these variables may be
considered for the development of biomarkers of AD. However, lymphocytes from ALS patients do not represent a useful model to study cell
cycle-related events associated with neurodegeneration of motoneurons. (IJCEP811004).

Key Words: Alzheimer’s disease, Amyotrophic Lateral Sclerosis, lymphocytes, cell proliferation, apoptosis, p21, p27, PI3K/Akt, ERK1/2

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Address all correspondence to: Dr. Ángeles Martín-Requero, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040
Madrid, SPAIN, Phone: 34-91-837-3112, Fax: 34-91-536-0432, Email: