title: Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance.
abstract: Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer's disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer's disease. In addition, impaired insulin signaling in the Alzheimer's disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis.
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Caihong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Schwarz
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Irina
authors.initials: I
authors.lastname: Abakumova
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D016229:Amyloid beta-Peptides; D007328:Insulin; D011328:Prions