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Lookup NU author(s): Dr Masafumi Ihara, Professor Raj KalariaORCiD
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Chronic cerebral ischemia may accelerate clinicopathological changes in Alzheimer's disease. We have examined whether chronic cerebral hypoperfusion accelerates amyloid beta deposition in amyloid protein precursor transgenic (APP-Tg) mouse. At 5, 8, and 11 months of age, C57Bl/6J male mice overexpressing a mutant form of the human APP bearing the both Swedish (K670N/M671L) and the Indiana (V717F) mutations (APPSwInd) and their litterrmates were subjected to either sham operation or bilateral carotid artery stenosis (BCAS) using microcoils with an internal diameter of 0.18 mm (short-period group). One month after the sham operation or BCAS, these animals were examined by immunohistochemistry for glial fibrillary acidic protein, amyloid beta(1-40) (A beta(1-40)), amyloid beta(1-42) (A beta(1-42)), as well as Western blotting and filter assay for A beta. Another batch of the littermates of APPSwInd mice were subjected to either sham operation or BCAS at 3 months and were examined in the same manner after survival for 9 months (long-period group). in the BCAS-treated group, the white matter was rarefied and astroglia was proliferated. Amyloid beta(1-40) immunoreactivity was found in a few axons in the white matter after BCAS, whereas A beta(1-42) was accumulated in the scattered cortical neurons and the axons at ages of 6 months and thereafter in the short- and long-period groups. In the neuropil, both A beta(1-40) and A beta(1-42) were deposited in the sham-operated and BCAS-treated mice at ages of 9 and 12 months. There were no differences between the short-period group at ages of 12 months and the long-period group. Filter assay showed an increase of A beta fibrils in the extracellular enriched fraction. Taken together, chronic cerebral hypoperfusion increased A beta fibrils and induced A beta deposition in the intracellular compartment and, therefore, may accelerate the pathological changes of Alzheimer's disease. (C) 2009 Elsevier B.V. All rights reserved.
Author(s): Kitaguchi H, Tomimoto H, Ihara M, Shibata M, Uemura K, Kalaria RN, Kihara T, Asada-Utsugi M, Kinoshita A, Takahashi R
Publication type: Article
Publication status: Published
Journal: Brain Research
Year: 2009
Volume: 1294
Pages: 202-210
ISSN (print): 0006-8993
ISSN (electronic): 1872-6240
Publisher: Elsevier BV
URL: http://dx.doi.org/10.1016/j.brainres.2009.07.078
DOI: 10.1016/j.brainres.2009.07.078
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