Gene expression associated with Alzheimer's Disease in brain patients samples and controls using the PCR real-time technique

• Grant number: 15/24699-9
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2016
• End date: September 30, 2018
• Field of knowledge: Biological Sciences - Morphology
• Principal Investigator: Spencer Luiz Marques Payão
• Grantee: Spencer Luiz Marques Payão
• Host Institution: Faculdade de Medicina de Marília (FAMEMA). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). Marília , SP, Brazil
• Associated researchers: Elizabeth Suchi Chen ; Lucas Trevizani Rasmussen ; Marilia de Arruda Cardoso Smith

Abstract

Alzheimer's disease is a neurodegenerative, irreversible and progressive disorder, that is characterized by cognition's decline, loss of memory and mental confusion. It most commonly occurs after age 60, may also have its start earlier at age 40. In AD, mutations in three genes are associated with the main disease; precursor protein gene of ²-amyloid (A²PP), presenilin 1 gene (PS1) gene and presenilin 2 (PS2). The E4 allele of the apolipoprotein E gene (ApoE4), has also been associated with AD and is considered the major genetic risk factor for disease. It is suggested that mutations in the aforementioned genes can be related to alterations in the expression and subsequent accumulation of such deposits and the b-amyloid peptide (Ab), forming senile plaques, major histological findings in the brain of AD patients. It is believed that beta amyloid precursor protein A4, Apolipoprotein E, presenilins 1 and 2, family member 2 (APBA2), membrane glycoprotein found primarily in the brain, the LDL receptor gene related protein 1 (LRP1), the glutamatergic system gene (GRIN2D), the Gap junction beta 1 (GJB1) can modulate the production of APP fragments in senile plaques, but studies involving some of these genes are inconclusive to date and performed separately, and there is no article specific that compare the expression among them in the brains of AD patients in the comparative point of view, idealizing a correlation study considering these genes. In similarity, the role of insulin and its receptor (INSR) in the brain is still unclear, however, knowing it is beneficial relationships important in learning and memory to modulate synaptic functions. Therefore, this project aims to: analyze the expression of regulatory genes of APP, and glucose metabolism mentioned above, by means of real-time PCR in cerebellum samples and auditory cortex of patients with AD and controls. The development of this approach may open new perspectives for the characterization of factors involved in gene regulation, as well as better understanding on the interaction of key genes involved in AD order in the near future, obtaining possible markers for Alzheimer's disease and perhaps strategies therapies. (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)

FUKASAWA, JOSIANNE T.; DE LABIO, ROGER W.; RASMUSSEN, LUCAS T.; DE OLIVEIRA, LUCIENI C.; CHEN, ELIZABETH; VILLARES, JOAO; TURECK, GUSTAVO; SMITH, MARILIA DE ARRUDA C.; PAYAO, SPENCER L. M.. CDK5 and MAPT Gene Expression in Alzheimer's Disease Brain Samples. Current Alzheimer Research, v. 15, n. 2, p. 182-186, 2018. (09/15857-9, 15/24699-9)