title: Long-term exposition to a high fat diet favors the appearance of β-amyloid depositions in the brain of C57BL/6J mice. A potential model of sporadic Alzheimer's disease.
abstract: The sporadic and late-onset form of Alzheimer's disease (AD) constitutes the most common form of dementia. This non-familiar form could be a consequence of metabolic syndrome, characterized by obesity and the development of a brain-specific insulin resistance known as type III diabetes. This work demonstrates the development of a significant AD-like neuropathology due to these metabolic alterations.
  
  
  
  C57BL/6J mice strain were divided into two groups, one fed with a diet rich in palmitic acid (high-fat diet, HFD) since their weaning until 16 months of age, and another group used as a control with a regular diet. The analyses were carried out in the dentate gyrus area of the hippocampus using a Thioflavin-S stain and immunofluorescence assays.
  
  
  
  The most significant finding of the present research was that HFD induced the deposition of the βA peptide. Moreover, the diet also caused alterations in different cell processes, such as increased inflammatory reactions that lead to a decrease in the neuronal precursor cells. In addition, the results show that there were also dysregulations in normal autophagy and apoptosis, mechanisms related to βA formation.
  
  
  
  The present findings confirm that HFD favors the formation of βA depositions in the brain, a key feature of AD, supporting the metabolic hypothesis of sporadic AD.
authors.affiliation: Departament de Bioquímica i Biotecnologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Tarragona, Spain; Departament de Farmacologia, Toxicologia i Quimica Terapeurica, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Busquets
authors.affiliation: Departament de Farmacologia, Toxicologia i Quimica Terapeurica, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Ettcheto
authors.affiliation: Departament de Farmacologia, Toxicologia i Quimica Terapeurica, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Insitutut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Pallàs
authors.affiliation: Laboratorio de Regeneración y Desarrollo Neural, Instituto de Neurobiología, Departamento de Biología Celular y Molecular, CUCBA, Guadalajara, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Beas-Zarate
authors.affiliation: Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Insitutut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Verdaguer
authors.affiliation: Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Insitutut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Auladell
authors.affiliation: Departament de Bioquímica i Biotecnologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Tarragona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Folch
authors.affiliation: Departament de Farmacologia, Toxicologia i Quimica Terapeurica, Facultat de Farmàcia i Ciències de l'Alimentació, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Insitutut de Neurociències, Universitat de Barcelona, Barcelona, Spain. Electronic address: camins@ub.edu.
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice
chemical_list: D016229:Amyloid beta-Peptides; D004041:Dietary Fats
keywords: AD; AMP-activated protein kinase; AMPK; ANS; Alzheimer’s disease; Aβ; BACE1; BBB; CSF; DIO; HCD; HFD; IGF-1; LOAD; MAPK; PTP1β; T2DM; autonomic nervous system; beta-site APP-cleaving enzyme 1; brain blood barrier; cerebrospinal fluid; diet-induced obesity; high calorie diet; high-fat diet; insulin-like growth factor-1; late-onset Alzheimer’s disease; mitogen-activated protein kinase; protein tyrosine phosphatase 1β; type 2 diabetes mellitus; β-amyloid