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Pharmaceuticals 2018, 11(1), 11; doi:10.3390/ph11010011

The Implication of the Brain Insulin Receptor in Late Onset Alzheimer’s Disease Dementia

Departament de Bioquímica i Biotecnologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, 43201 Reus, Spain
Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain
Departament de Farmacologia, Toxicologia i Química Terapèutica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Av. Joan XXIII 27/31, E-08028 Barcelona, Spain
Institut de Neurociències, Universitat de Barcelona, E-08028 Barcelona, Spain
Unitat de Farmàcia, Tecnologia Farmacèutica i Fisico-química, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, E-08028 Barcelona, Spain
Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Barcelona E-08028, Spain
Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, E-08028 Barcelona, Spain
Laboratorio de Regeneración y Desarrollo Neural, Instituto de Neurobiología, Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan 44600, Mexico
Department of Gerontology, Federal University of São Carlos (UFSCar), São Carlos 13565-905, Brazil
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca 3460000, Chile
Author to whom correspondence should be addressed.
Received: 29 December 2017 / Revised: 24 January 2018 / Accepted: 25 January 2018 / Published: 29 January 2018
(This article belongs to the Special Issue Epilepsy and Neurodegeneration: Current Therapeutic Implications)
View Full-Text   |   Download PDF [920 KB, uploaded 29 January 2018]   |  


Alzheimer’s disease (AD) is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid β peptide (Aβ), which form senile plaques, neurofibrillary tangles (NFT) and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM) and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline. Brain insulin resistance, also known as Type 3 diabetes, leads to the increase of Aβ production and TAU phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, and cognitive impairment, which are all hallmarks of AD. Moreover, given the complexity of interlocking mechanisms found in late onset AD (LOAD) pathogenesis, more data is being obtained. Recent evidence showed that Aβ42 generated in the brain would impact negatively on the hypothalamus, accelerating the “peripheral” symptomatology of AD. In this situation, Aβ42 production would induce hypothalamic dysfunction that would favour peripheral hyperglycaemia due to down regulation of the liver insulin receptor. The objective of this review is to discuss the existing evidence supporting the concept that brain insulin resistance and altered glucose metabolism play an important role in pathogenesis of LOAD. Furthermore, we discuss AD treatment approaches targeting insulin signalling using anti-diabetic drugs and mTOR inhibitors. View Full-Text
Keywords: Alzheimer’s; insulin resistance; amyloid; TAU; cognition; insulin receptor; type 2 diabetes Alzheimer’s; insulin resistance; amyloid; TAU; cognition; insulin receptor; type 2 diabetes

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Folch, J.; Ettcheto, M.; Busquets, O.; Sánchez-López, E.; Castro-Torres, R.D.; Verdaguer, E.; Manzine, P.R.; Poor, S.R.; García, M.L.; Olloquequi, J.; Beas-Zarate, C.; Auladell, C.; Camins, A. The Implication of the Brain Insulin Receptor in Late Onset Alzheimer’s Disease Dementia. Pharmaceuticals 2018, 11, 11.

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