Researchers from Inserm and the Université Lille/Université Lille Nord de France have recently used a neurodegeneration model of Alzheimer’s disease to provide experimental evidence of the relationship between obesity and disorders linked to the tau protein. This research was conducted on mice and is published in the Diabetes review: it corroborates the theory that metabolic anomalies contribute massively to the development of dementia.
In France, more than 860,000 people suffer from Alzheimer’s disease and related disorders, making them the largest cause of age-related loss of intellectual function. Cognitive impairments observed in Alzheimer’s disease result from the accumulation of abnormal tau proteins in nerve cells undergoing degeneration (see the picture below). We know that obesity, a major risk factor in the development of insulin resistance and type 2 diabetes, increases the risk of dementia during the aging process. However, the effects of obesity on ‘Taupathies’ (i.e. tau protein-related disorders), including Alzheimer’s disease, were not clearly understood. In particular, researchers assumed that insulin resistance played a major role in terms of the effects of obesity.
The “Alzheimer & Tauopathies” team from mixed research unit 837 (Inserm/Université Lille 2/Université Lille Nord de France) directed by Dr. Luc Buée, in collaboration with mixed research unit 1011 “Nuclear receptors, cardiovascular diseases and diabetes”, have just demonstrated, in mice, that obese subjects develop aggravated disorders. To achieve this result, young transgenic mice, who develop tau-related neurodegeneration progressively with age, were put on a high-fat diet for five months, leading to progressive obesity.
“At the end of this diet, the obese mice had developed an aggravated disorder both from the point of view of memory and modifications to the Tau protein”
explains David Blum, in charge of research at Inserm.
This study uses a neurodenegeneration model of Alzheimer’s disease to provide experimental evidence of the relationship between obesity and disorders linked to the tau protein. Furthermore, it indicates that insulin resistance is not the aggravating factor, as was suggested in previous studies.
“Our research supports the theory that environmental factors contribute massively to the development of this neurodegenerative disorder” underlines the researcher. “Our work is now focussing on identifying the factors responsible for this aggravation” he adds.
The degeneration of neurons in Alzheimer’s disease
Chargé de recherche Inserm UMR 837 "Centre de recherche Jean Pierre Aubert – JPArc" (Inserm/ Univ. Lille-Nord de France, UDSL)
Equipe "Alzheimer & Tauopathies" – LabEx DISTALZ
Faculté de Médecine-Pôle Recherche
Institut de Médecine Prédictive et Recherche Thérapeutique
59045 Lille France
Tel: 03 20 29 88 58
Detrimental Effects of Diet-Induced Obesity on τ Pathology Is Independent of Insulin Resistance in τ Transgenic Mice
Antoine Leboucher 1,2, Cyril Laurent1,2, Francisco-José Fernandez-Gomez 1,2, Sylvie Burnouf 1,2, Laetitia Troquier 1,2, Sabiha Eddarkaoui 1,2, Dominique Demeyer 1,2, Raphaëlle Caillierez 1,2, Nadège Zommer 1,2, Emmanuelle Vallez 1,3,4, Kadiombo Bantubungi 1,3,4, Christophe Breton 1,5, Pascal Pigny 1,2,6, Valérie Buée-Scherrer 1,2, Bart Staels 1,3,4, Malika Hamdane 1,2, Anne Tailleux 1,3,4, Luc Buée 1,2,6 and David Blum1,2,6
1Université Lille-Nord de France, Université du Droit et de la Santé de Lille, Lille, France
2INSERM U837, Jean-Pierre Aubert Research Centre, Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France
3INSERM U1011, Lille, France
4Institut Pasteur de Lille, Lille, France
5EA 4489, Environnement Perinatal et Croissance, Lille, France
6Centre Hospitalier Régional Universitaire de Lille, Lille, France
Diabetes décembre 2012 doi: 10.2337/db12-0866