Japanese Journal of National Medical Services
Online ISSN : 1884-8729
Print ISSN : 0021-1699
ISSN-L : 0021-1699
A HYPOTHESIS CONCERNING DISTURBED AXOPLASMIC FLOW AS A COMMON PATHOGENIC MECHANISM LINKING AMYLOIDOGENESIS AND TANGLE FORMATION OF ALZHEIMER'S DISEASE
Kazuo SHIGEMATSUHiroshi SUGIYAMAPatrick L. MCGEER
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1993 Volume 47 Issue 12 Pages 954-959

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Abstract
The relationship between the two outstanding pathologic hallmarks of Alzheimer's disease, intracellular neurofibrillary tangles and extracellular amyloid deposits, is still a mystery. Tangles are partly characterized by argentophilicity and Alz-50 positivity, while amyloid deposits are characterized by accumulations of beta-amyloid precursor protein (APP). We hypothesized that a disturbance of axoplasmic flow may be the common pathogenic mechanism linking these main two pathological entities. To test this hypothesis, we injected kainic acid, colchicine, or aluminum salts into rat brain as independent methods of damaging neuron and interfering with axoplasmic flow. We then examined brain sections by silver staining and by immunohistochemical staining for APP and Alz-50. With each injection, affected neurons accumulated APP within hours and showed Alz-50 immunopositivity as well as an argentophilic reaction. After several days, APP immunoreactivity was seen extraneurally, some within phagocytosing reactive microglia. These results support the hypothesis that an interference with axoplasmic flow could link cytoskeletal abnormalities and APP accumulation.
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© Japanese Society of National Medical Services
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