The pathological interaction between diabetes and presymptomatic Alzheimer's disease.

Abstract:

:Since diabetes is a risk factor for Alzheimer's disease (AD), we asked if there is a functional interaction between high glucose and elevated beta amyloid peptide (Abeta) in cultured brain microvascular endothelial cells and presymptomatic AD transgenic mice. When cultured brain microvascular endothelial cells are exposed to both high glucose and low levels of Abeta, there is a synergistic interaction to cause an increased accumulation of advanced glycation products (AGE) and reactive oxygen species (ROS). When presymptomatic mice expressing mutant human amyloid precursor protein and presenilin are made diabetic, they have a decrease in cognitive function relative to control mice. Associated with the cognitive deficit are increases in brain microvascular AGE and iNOS expression, and the loss of the synaptic spine protein drebrin. No amyloid plaques or tangles are observed within the brains of any group. These data show that diabetes causes a synergistic potentiation of some indices of AD in transgenic animals that are presymptomatic for the classical features of the disease.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Burdo JR,Chen Q,Calcutt NA,Schubert D

doi

10.1016/j.neurobiolaging.2008.02.010

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

1910-7

issue

12

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(08)00059-6

journal_volume

30

pub_type

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