title: Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and Alzheimer's disease.
abstract: There is an increasing awareness that diabetes has an impact on the CNS and that diabetes is a risk factor for Alzheimer's disease (AD). Links between AD and diabetes point to impaired insulin signaling as a common mechanism leading to defects in the brain. However, diabetes is predominantly characterized by peripheral, rather than central, neuropathy, and despite the common central mechanisms linking AD and diabetes, little is known about the effect of AD on the peripheral nervous system (PNS). In this study, we compared indexes of peripheral neuropathy and investigated insulin signaling in the sciatic nerve of insulin-deficient mice and amyloid precursor protein (APP) overexpressing transgenic mice. Insulin-deficient and APP transgenic mice displayed similar patterns of peripheral neuropathy with decreased motor nerve conduction velocity, thermal hypoalgesia, and loss of tactile sensitivity. Phosphorylation of the insulin receptor and glycogen synthase kinase 3β (GSK3β) was similarly affected in insulin-deficient and APP transgenic mice despite significantly different blood glucose and plasma insulin levels, and nerve of both models showed accumulation of Aβ-immunoreactive protein. Although diabetes and AD have different primary etiologies, both diseases share many abnormalities in both the brain and the PNS. Our data point to common deficits in the insulin-signaling pathway in both neurodegenerative diseases and support the idea that AD may cause disorders outside the higher CNS.
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA, USA. cjolivalt@ucsd.edu
authors.forename: C G
authors.initials: CG
authors.lastname: Jolivalt
authors.forename: N A
authors.initials: NA
authors.lastname: Calcutt
authors.forename: E
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009431:Neural Conduction / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000473:pathology*; D010766:Phosphorylation; D020426:Sciatic Neuropathy / Q000473:pathology; D012684:Sensory Thresholds / Q000502:physiology; D013697:Thermosensing / Q000502:physiology; D014110:Touch / Q000502:physiology; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse