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.
journal_name
Proc Natl Acad Sci U S Aauthors
Colton CA,Vitek MP,Wink DA,Xu Q,Cantillana V,Previti ML,Van Nostrand WE,Weinberg JB,Dawson Hdoi
10.1073/pnas.0601075103subject
Has Abstractpub_date
2006-08-22 00:00:00pages
12867-72issue
34eissn
0027-8424issn
1091-6490pii
0601075103journal_volume
103pub_type
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