Reduction of acetylated alpha-tubulin immunoreactivity in neurofibrillary tangle-bearing neurons in Alzheimer's disease.
A disturbance of the microtubule network in neurons containing neurofibrillary tangles (NFT), one of the characteristic neuropathological lesions in Alzheimer's disease, has been advocated as a central physiopathological mechanism leading to neuronal dysfunction in NFT-containing neurons. The accumulation of "paired helical filament-tau," the main proteineous component of NFT, in affected neurons has been proposed to induce a decrease of microtubule stability in these cells. To further explore the hypothesis of a decrease in microtubule stability in Alzheimer's disease, we have investigated in this study the relative content in stable microtubules in neurons with different amount of NFT. We used a double immunocytochemical labeling technique with antibodies to tau (as a marker of NFT) and to acetylated alpha-tubulin (as a marker of stable microtubules) and rated on a semi-quantitative scale the tau and acetylated alpha-tubulin-immunoreactivities in the same neurons. We observed a strong reduction in acetylated alpha-tubulin immunoreactivity in most NFT-bearing neurons; a statistical relationship between tau and acetylated alpha-tubulin immunoreactivity was demonstrated, assuming an inverse relationship between the presence of tau-immunoreactive NFT and tubulin-immunoreactivity in neurons. This reduction was already seen in the neuronal population with a relatively lower tau-immunoreactivity, suggesting that reduction in acetylated alpha-tubulin immunoreactivity, and reduction in microtubule stability, could be an early event in these cells.
Hempen
B
B
Laboratory of Pathology and Electron Microscopy, Université Libre de Bruxelles, Faculté de Medicine, Belgium.
Brion
J P
JP
D000107:Acetylation; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000918:Antibody Specificity; D002452:Cell Count; D003627:Data Interpretation, Statistical; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D008870:Microtubules / Q000737:chemistry; D016874:Neurofibrillary Tangles / Q000737:chemistry*; D009474:Neurons / Q000737:chemistry* / Q000166:cytology; D017966:Pyramidal Cells / Q000737:chemistry / Q000166:cytology; D014404:Tubulin / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D016875:tau Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism
D014404:Tubulin; D016875:tau Proteins