Exclusive association and simultaneous appearance of congophilic plaques and AT8-positive dystrophic neurites in Tg2576 mice suggest a mechanism of senile plaque formation and progression of neuritic dystrophy in Alzheimer's disease

Acta Neuropathologica
Kyoko Noda-SaitaTokio Yamaguchi

Abstract

Progression of neuritic dystrophy is a histological hallmark of Alzheimer's disease (AD) in addition to amyloid deposition and neurofibrillary tangle formation. Dystrophic neurites (DNs) are abnormal neurites, and are closely associated with amyloid deposits. To clarify the process of DN formation, we immunohistochemically investigated phosphorylated tau (AT8 and Ser396)-positive DNs and plaques in Tg2576 mice overexpressing human beta-amyloid precursor protein (APP) with the Swedish type mutation (K670N/M671L). AT8-positive DNs were exclusively associated with the Congo red-positive plaques examined, and all Abeta(1-40)-positive plaques appeared to be associated with AT8-positive DNs, whereas there were no AT8-positive DNs with Abeta(1-42)-positive/Abeta(1-40)-negative plaques. Since we have previously shown that Abeta(1-42)-positive plaque precede Abeta(1-40) deposition, the appearance of congophilic structures is also late. Quantitative analyses were performed on AT8-positive DNs that were associated with congophilic plaques in the cerebral cortex and hippocampus (more than 1,000 plaques). The number of congophilic plaques increased dramatically with age. The area of DNs in the cerebral cortex and hippocampus increased 120- ...Continue Reading

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Citations

May 29, 2008·Proceedings of the National Academy of Sciences of the United States of America·Francesca CacucciJohn O'Keefe
Mar 1, 2006·Journal of Neuroinflammation·Vincent LaporteMichael Mullan
Aug 28, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Juliet K KnowlesFrank M Longo
Oct 24, 2007·Neurobiology of Aging·Adele WoodhouseTracey C Dickson
Jan 7, 2010·Journal of Neurochemistry·Maria Cristina RosiFiorella Casamenti
Sep 16, 2009·Biochimica Et Biophysica Acta·Jürgen GötzLars M Ittner
Jan 11, 2005·Neurotoxicity Research·Adele WoodhouseTracey C Dickson

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