Evaluation of symptomatic and asymptomatic Alzheimer's Disease in post-mortem human brains

• Grant number: 11/01652-6
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2011 - June 30, 2013
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Helena Paula Brentani
• Grantee: Helena Paula Brentani
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil

Abstract

Alzheimer's disease (AD) is characterized by a progressive decline in cognition associated with the accumulation of amyloid ²-peptides (senile plaques), hyperphosphorylated tau protein (neurofibrillary tangles), synaptic degeneration and neuronal death in hippocampus and other cortical regions. Recent evidences have pointed that the neurodegeneration in AD is related to the activation of cell cycle in post-mitotic neurons, and aneuploidic cells can be result of cell cycle reentry with subsequent total or partial replication of neuronal DNA, being these cells potentially associated with cell death. Oxidative stress have also been pointed as an important factor in the pathogenesis of neurodegenerative diseases, since it can induce DNA damage, and the repair mechanisms can be impaired in AD. Furthermore, there are individuals that fulfill the AD neuropathological criteria, but do not display cognitive deficit (asymptomatic AD), representing individuals protected in some way (cognitive reserve). Given this, it is not clear how the nervous system behaves within the same injuries. Therefore, this work is aiming to differentiate - using techniques for evaluation of both protein and gene expression - subjects with symptomatic and asymptomatic DA, and healthy normal individuals in relation to cell cycle, synaptic plasticity, damage and DNA repair, cell death and aneuploidy. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, ADERBAL R. T.; FEIO SANTOS, ANA CECILIA; FARFEL, JOSE M.; GRINBERG, LEA T.; FERRETTI, RENATA E. L.; FROES MARQUES CAMPOS, ANTONIO HUGO JOSE; CUNHA, ISABELA WERNECK; BEGNAMI, MARIA DIRLEI; ROCHA, RAFAEL M.; CARRARO, DIRCE M.; et al. Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer's Disease. PLoS One, v. 9, n. 6, JUN 17 2014. (11/01652-6, 09/02030-9, 09/01527-7)