Increased tau phosphorylation and cleavage in mouse models of type 1 and type 2
Authors Kim B, Backus C, Oh S, Hayes JM, Feldman EL
Submitted By Eva Feldman on 3/24/2010
Status Published
Journal Endocrinology
Year 2009
Date Published 12/1/2009
Volume : Pages 150(12) : 5294 - 5301
PubMed Reference 19819959
Abstract As the population of the United States ages, the incidence of age-related
neurodegenerative and systemic diseases including Alzheimer's disease (AD) and
diabetes is increasing rapidly. Multiple studies report that patients with
diabetes have a 50-75% increased risk of developing AD compared with age- and
gender-matched patients without diabetes. Abnormally phosphorylated tau is a
major building block of neurofibrillary tangles, a classic neuropathological
characteristic of AD. In addition, proteolytic tau cleavage promotes AD
progression due to cleaved tau serving as a nucleation center for the
pathological assembly of tau filaments. The current study examines tau
modification in type 1 (streptozotocin-injected) and type 2 (db/db) mouse models
of diabetes. Tau phosphorylation is increased in the cortex and hippocampus of
db/db mice compared with db+ control mouse brain. Interestingly, there is an
age-dependent increase in tau cleavage that is not observed in age-matched
control db+ animals. Streptozotocin injection also increased tau
phosphorylation; however, the increase was less significant compared with the
type 2 mouse model, and more importantly, no tau cleavage was detected. Our
results suggest tau modification caused by insulin dysfunction and hyperglycemia
may contribute to the increased incidence of AD in diabetes. We hypothesize that
type 1 and type 2 diabetes may contribute to AD through different mechanisms; in
type 2 diabetes, hyperglycemia-mediated tau cleavage may be the key feature,
whereas insulin deficiency may be the major contributing factor in type 1

Investigators with authorship
Eva FeldmanUniversity of Michigan


Csnk1ecasein kinase 1, epsilon
Maptmicrotubule-associated protein tau