BetaII-tubulin and phospho-tau aggregates in Alzheimer's disease and Pick's disease

TY - JOUR

T1 - BetaII-tubulin and phospho-tau aggregates in Alzheimer's disease and Pick's disease

AU - Puig, B

AU - Ferrer, I

AU - Ludueña, R F

AU - Avila, J

AU - Puig Martorell, Berta

PY - 2005/6/1

Y1 - 2005/6/1

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Brain

KW - Dentate Gyrus

KW - Entorhinal Cortex

KW - Female

KW - Humans

KW - Male

KW - Nerve Tissue Proteins

KW - Neurofibrillary Tangles

KW - Neuroglia

KW - Neurons

KW - Phosphorylation

KW - Pick Disease of the Brain

KW - Protein Isoforms

KW - Tauopathies

KW - Tubulin

KW - tau Proteins

M3 - SCORING: Journal article

C2 - 16006664

VL - 7

SP - 213-20; discussion 255-62

JO - J ALZHEIMERS DIS

JF - J ALZHEIMERS DIS

SN - 1387-2877

IS - 3

ER -