Hyperglycemia-induced Tau cleavage in vitro and in vivo: a possible link between
diabetes and Alzheimer's disease.
Authors Kim B, Backus C, Oh S, Feldman EL
Submitted By Eva Feldman on 7/10/2013
Status Published
Journal Journal of Alzheimer's disease : JAD
Year 2013
Date Published 12/1/2012
Volume : Pages 34 : 727 - 739
PubMed Reference 23254634
Abstract Multiple lines of evidence link the incidence of diabetes to the development of
Alzheimer's disease (AD). Patients with diabetes have a 50 to 75% increased risk
of developing AD. In parallel, AD patients have a higher than normal tendency to
develop type 2 diabetes or impaired fasting glucose. Tau is the major component
of neurofibrillary tangles, one of the hallmarks of AD pathology. The current
study examined the effect of hyperglycemia on tau modification. Glucose
treatment of rat embryonic cortical neurons results in concentration-dependent
apoptosis and caspase-3 activation. These changes are well correlated with
glucose time- and concentration-dependent tau cleavage. Aß treatment induces tau
cleavage and when added together with glucose, there is an additive effect on
caspase activation, apoptosis, and tau cleavage. Tau cleavage is partially
blocked by the caspase inhibitor, ZVAD. Cleaved tau displays a punctate staining
along the neurites and colocalizes with cleaved caspase-3 in the cytoplasm. Both
type 1 and type 2 diabetic mice display increased tau phosphorylation in the
brain. In agreement with the effects of glucose on tau modifications in vitro,
there is increased tau cleavage in the brains of ob/ob mice; however, tau
cleavage is not observed in type 1 diabetic mouse brains. Our study demonstrates
that hyperglycemia is one of major factors that induce tau modification in both
in vitro and in vivo models of diabetes. We speculate that tau cleavage in
diabetic conditions (especially in type 2 diabetes) may be a key link for the
increased incidence of AD in diabetic patients.

Investigators with authorship
Eva FeldmanUniversity of Michigan