NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease.

Abstract:

:Alzheimer's disease is characterized by two primary pathological features: amyloid plaques and neurofibrillary tangles. The interconnection between amyloid and tau aggregates is of intense interest, but mouse models have yet to reveal a direct interrelationship. We now show that NO may be a key factor that connects amyloid and tau pathologies. Genetic removal of NO synthase 2 in mice expressing mutated amyloid precursor protein results in pathological hyperphosphorylation of mouse tau, its redistribution to the somatodendritic compartment in cortical and hippocampal neurons, and aggregate formation. Lack of NO synthase 2 in the amyloid precursor protein Swedish mutant mouse increased insoluble beta-amyloid peptide levels, neuronal degeneration, caspase-3 activation, and tau cleavage, suggesting that NO acts at a junction point between beta-amyloid peptides, caspase activation, and tau aggregation.

authors

Colton CA,Vitek MP,Wink DA,Xu Q,Cantillana V,Previti ML,Van Nostrand WE,Weinberg JB,Dawson H

doi

10.1073/pnas.0601075103

subject

Has Abstract

pub_date

2006-08-22 00:00:00

pages

12867-72

issue

34

eissn

0027-8424

issn

1091-6490

pii

0601075103

journal_volume

103

pub_type

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