Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and
Alzheimer's disease.
Authors Jolivalt CG, Calcutt NA, Masliah E
Submitted By Nigel Calcutt on 1/30/2013
Status Published
Journal Neuroscience
Year 2012
Date Published 1/27/2012
Volume : Pages 202 : 405 - 412
PubMed Reference 22178988
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 3ß (GSK3ß) 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 Aß-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.

Investigators with authorship
Nigel CalcuttUniversity of California San Diego