title: Posttranslational modifications of α-tubulin in alzheimer disease.
abstract: BACKGROUND
  In Alzheimer disease (AD), hyperphosphorylation of tau proteins results in microtubule destabilization and cytoskeletal abnormalities. Our prior ultra-morphometric studies documented a clear reduction in microtubules in pyramidal neurons in AD compared to controls, however, this reduction did not coincide with the presence of paired helical filaments. The latter suggests the presence of compensatory mechanism(s) that stabilize microtubule dynamics despite the loss of tau binding and stabilization. Microtubules are composed of tubulin dimers which are subject to posttranslational modifications that affect the stability and function of microtubules.
  
  
  METHODS
  In this study, we performed a detailed analysis on changes in the posttranslational modifications in tubulin in postmortem human brain tissues from AD patients and age-matched controls by immunoblot and immunocytochemistry.
  
  
  RESULTS
  Consistent with our previous study, we found decreased levels of α-tubulin in AD brain. Levels of tubulin with various posttranslational modifications such as polyglutamylation, tyrosination, and detyrosination were also proportionally reduced in AD brain, but, interestingly, there was an increase in the proportion of the acetylated α-tubulin in the remaining α-tubulin. Tubulin distribution was changed from predominantly in the processes to be more accumulated in the cell body. The number of processes containing polyglutamylated tubulin was well preserved in AD neurons. While there was a cell autonomous detrimental effect of NFTs on tubulin, this is likely a gradual and slow process, and there was no selective loss of acetylated or polyglutamylated tubulin in NFT-bearing neurons.
  
  
  CONCLUSIONS
  Overall, we suggest that the specific changes in tubulin modification in AD brain likely represent a compensatory response.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44121 USA.|Department of Neurosurgery, Shandong Provincial Hospital, Shandong University, Jinan, 250012 China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Shandong University, Jinan, 250012 China.
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44121 USA.|Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44121 USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Siedlak
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México Querétaro, Querétaro México, D. F. Mexico.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Mondragon-Rodriguez
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44121 USA.
authors.forename: Hyoung-Gon
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44121 USA.
authors.forename: Xinglong
authors.initials: X
authors.lastname: Wang
authors.affiliation: The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249 USA.
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44121 USA.|2103 Cornell Road, Cleveland, OH 44106 USA.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
keywords: Acetylation; Alzheimer disease; Polyglutamylation; Tau; Tubulin