title: Regional Increase in the Expression of the BCAT Proteins in Alzheimer's Disease Brain: Implications in Glutamate Toxicity.
abstract: BACKGROUND
  The human branched chain aminotransferases (hBCATm, mitochondrial and hBCATc, cytosolic) are major contributors to brain glutamate production. This excitatory neurotransmitter is thought to contribute to neurotoxicity in neurodegenerative conditions such as Alzheimer's disease (AD) but the expression of hBCAT in this disease has not previously been investigated.
  
  
  OBJECTIVE
  The objective of investigating hBCAT expression is to gain insight into potential metabolic pathways that may be dysregulated in AD brain, which would contribute to glutamate toxicity.
  
  
  METHODS
  Western blot analysis and immunohistochemistry were used to determine the expression and localization of hBCAT in postmortem frontal and temporal cortex from AD and matched control brains.
  
  
  RESULTS
  Western blot analysis demonstrated a significant regional increase in hBCATc expression in the hippocampus (↑ 36%; p-values of 0.012), with an increase of ↑ 160% reported for hBCATm in the frontal and temporal cortex (p-values = 4.22 × 10⁻⁴ and 2.79 × 10⁻⁵, respectively) in AD relative to matched controls, with evidence of post-translational modifications to hBCATm, more prominent in AD samples. Using immunohistochemistry, a significant increase in immunopositive labelling of hBCATc was observed in the CA1 and CA4 region of the hippocampus (p-values = 0.011 and 0.026, respectively) correlating with western blot analysis. Moreover, the level of hBCATm in the frontal and temporal cortex correlated significantly with disease severity, as indicated by Braak staging (p-values = 5.63 × 10⁻⁶ and 9.29 × 10⁻⁵, respectively).
  
  
  CONCLUSIONS
  The expression of the hBCAT proteins is significantly elevated in AD brain. This may modulate glutamate production and toxicity, and thereby play a role in the pathogenesis of the disease.
authors: Faculty of Health and Life Sciences, University of the West of England, Bristol, UK.
authors: Jonathon
authors: J
authors: Hull
authors: Faculty of Science and Technology, University of Westminster, London, UK.
authors: Vinood
authors: V
authors: Patel
authors: Faculty of Health and Life Sciences, University of the West of England, Bristol, UK.
authors: Maya
authors: M
authors: El Hindy
authors: Faculty of Health and Life Sciences, University of the West of England, Bristol, UK.
authors: Christopher
authors: C
authors: Lee
authors: Faculty of Health and Life Sciences, University of the West of England, Bristol, UK.
authors: Esther
authors: E
authors: Odeleye
authors: Faculty of Health and Life Sciences, University of the West of England, Bristol, UK.
authors: Mohammed
authors: M
authors: Hezwani
authors: Dementia Research Group, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK.
authors: Seth
authors: S
authors: Love
authors: Dementia Research Group, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK.
authors: Patrick
authors: P
authors: Kehoe
authors: Dementia Research Group, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK.
authors: Katy
authors: K
authors: Chalmers
authors: Faculty of Health and Life Sciences, University of the West of England, Bristol, UK.
authors: Myra
authors: M
authors: Conway
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D000637:Transaminases / Q000378:metabolism*
chemical_list: C490590:BCAT1 protein, human; D000637:Transaminases
keywords: Alzheimer's disease; glutamate metabolism; hBCAT