Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and Alzheimer's disease

• Published in: Neuroscience Vol. 202; pp. 405 - 412
• Main Authors: Jolivalt, C.G, Calcutt, N.A, Masliah, E
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 27.01.2012; Elsevier
• Subjects: Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; amyloid precursor protein; Animals; Biological and medical sciences; Blotting, Western; Brain Chemistry - physiology; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; diabetes; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Type 1 - pathology; Diabetic Neuropathies - pathology; diabetic neuropathy; Fundamental and applied biological sciences. Psychology; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Humans; Immunohistochemistry; insulin signaling; Male; Medical sciences; Mice; Mice, Transgenic; Nervous system (semeiology, syndromes); Neural Conduction - physiology; Neurology; Peripheral Nervous System Diseases - pathology; Phosphorylation; sciatic nerve; Sciatic Neuropathy - pathology; Sensory Thresholds - physiology; Thermosensing - physiology; Touch - physiology; Ubiquitin Thiolesterase - metabolism; Vertebrates: nervous system and sense organs; APP; amyloid β; full-length APP; subepidermal nerve plexus; peripheral nervous system; FL-APP; Aβ; insulin signaling; PNS; SNP; amyloid precursor protein; GSK3; intraepidermal nerve fiber; ethylenediaminetetraacetic acid; STZ; motor nerve conduction velocity; Alzheimer's disease; WT; AD; glycogen synthase kinase3; diabetic neuropathy; EDTA; PWT; MNCV; streptozotocin; IENF; wild type; paw withdrawal thresholds; diabetes; sciatic nerve; Endocrinopathy; Animal model; Pancreatic hormone; Nervous system diseases; Alzheimer disease; Diabetes mellitus; Rodentia; Insulin; Amyloid precursor protein; Cerebral disorder; Signal transduction; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Degenerative disease; Peripheral nerve disease; Sciatic nerve
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2011.11.032

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.