alexa Diabetes Effects in Alzheimer Disease: The Interactive Role of Insulin and Aβ Peptide
ISSN: 2161-0460

Journal of Alzheimers Disease & Parkinsonism
Open Access

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Review Article

Diabetes Effects in Alzheimer Disease: The Interactive Role of Insulin and Aβ Peptide

Maria Elisa de Oliveira Lanna1,2*, Maria Lucia Vellutini Pimentel2 and Sergio Augusto Pereira Novis2

1Department of Cognitive Disorders - 24a e 25a Infirmaries– Neurology Service - Professor Sergio Augusto Pereira Novis - Hospital Geral Santa Casa da Misericórdia do Rio de Janeiro (HSCMRJ), RJ, Brazil

2Neurology Service - 24a e 25a Infirmaries– HSCMRJ, RJ, Brazil

Corresponding Author:
Maria Elisa de Oliveira Lanna
- Enfermarias 24 e 25 Serviço de Neurologia
do Professor Sergio Augusto Pereira
Novis – HSCMRJ. Rua Santa Luzia
206 – Centro/Castelo. Cep: 20020-022
Rio de Janeiro, RJ, Brazil
Tel: 5 (21) 2540-0659
Fax: 55 (21) 2524-4424
E-mail: [email protected]

Received date: February 25, 2014; Accepted date: April 20, 2014; Published date: May 20, 2014

Citation: de Oliveira Lanna ME, Pimentel MLV, Novis SAP (2014) Diabetes Effects in Alzheimer Disease: The Interactive Role of Insulin and Aβ Peptide. J Alzheimers Dis Parkinsonism 4:151. doi: 10.4172/2161-0460.1000151

Copyright: © 2014 de Oliveira Lanna ME, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Insulin resistance, hyper-insulinemia and products associated to insulin metabolism can affect the amyloid cascade and promote the onset of Alzheimer`s disease or aggravate the condition, in early or old age regardless of the development of type 2 diabetes. The changes described in pathological studies and molecular research, classify two types of mechanism involved with cognitive impairment in these cases: one related to cerebrovascular events due the action of vascular risk factors, and the other more controversial, non-cerebrovascular mechanism involving the interaction of insulin with Aβ in the entorhinal cortex and hippocampus, as well as its synaptogenesis action that involves signaling of intracellular molecular paths in the modulating of neurotransmitters such as acetylcholine, norepinephrine and glutamate receptors. Based on a literature review, the role of insulin in the Central Nervous System is examined along with its participation in the amyloidogenesis process in progression to Alzheimer Disease. This review also addresses the consequence of chronic peripheral hyperinsulinemia, leading to down-regulation of insulin receptors in the blood-brain barrier and decreased insulin up-take, causing a state of central hypoinsulinism. This state interferes mainly in the process of Aβ degradation, emphasizing the role of the catalytic enzymes in Aβ clearance, particularly of the insulinase. Among others, increasing synaptic toxicity by disrupting PI3K/Akt inhibition of the GSK3 intracellular molecular pathway increasing tau phosphorylation, as well as PKC synaptogenesis signaling, causing clinical and anatomic changes that favor Alzheimer Disease.

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