BetaII-tubulin and phospho-tau aggregates in Alzheimer's disease and Pick's disease.
The expression of betaI-, betaII- and betaIII-tubulin isotypes was examined by immunohistochemistry in the entorhinal and transentorhinal cortices, hippocampus and dentate gyrus in normal human brains and in cases with Alzheimer's disease (AD), Pick's disease (PiD) and in argyrophilic grain disease (AGD). The results showed that betaII-tubulin predominated in the upper layers (mainly layer II) and betaIII-tubulin in the inner layers of the entorhinal and transentorhinal cortices in control brains. betaII-tubulin immunoreactivity was higher than betaIII-tubulin immunoreactivity in granular neurons of the dentate gyrus, whereas pyramidal neurons of the hippocampus proper were stained equally with anti-betaII-tubulin andbetaIII-tubulin antibodies. No preferential layering distribution was observed for betaI-tubulin. Polymerization assays with tubulin peptides following the method of microtubule-associated protein displacement demonstrated that the betaI and betaIII isotypes have a higher binding capacity for tau than does the betaII isotype. Interestingly, about 60% of neurons with neurofibrillary tangles in layer II of the entorhinal and transentorhinal cortices in AD were selectively stained with anti-betaII-tubulin antibodies. Moderate betaII-tubulin immunoreactivity was also observed in Pick bodies in PiD. Taken together, these findings support the view that high betaII-tubulin content is a contributing factor in the formation of abnormal hyper-phosphorylated tau aggregates.
Puig
B
B
Instituto de Neuropatología, IDIBELL-Hospital Universitario de Bellvitge, Spain.
Ferrer
I
I
Ludueña
R F
RF
Avila
J
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D018891:Dentate Gyrus / Q000473:pathology; D018728:Entorhinal Cortex / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis*; D016874:Neurofibrillary Tangles / Q000473:pathology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons; D010766:Phosphorylation; D020774:Pick Disease of the Brain / Q000473:pathology*; D020033:Protein Isoforms / Q000032:analysis; D024801:Tauopathies / Q000473:pathology; D014404:Tubulin / Q000032:analysis*; D016875:tau Proteins
C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D014404:Tubulin; D016875:tau Proteins