Deposition of Alzheimer's vascular amyloid-β is associated with decreased expression of brain L-3-hydroxyacyl-coenzyme A dehydrogenase (ERAB)

Janusz Frackowiak, Bozena Mazur-Kolecka, Wojciech Kaczmarski, Dennis Dickson

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

L-3-hydroxyacyl-coenzyme A dehydrogenase type II (HADH) was described as an endoplasmic reticulum amyloid β-peptide-binding protein (ERAB), which enhances Aβ toxicity, and accumulates in neurons in Alzheimer's disease (AD). Hence, HADH/ERAB was suggested to mediate the amyloid-induced neurodegeneration. We estimated the in vivo interactions of HADH and Aβ in an immunocytochemical study of ten Alzheimer's disease and seven normal brains using five monoclonal HADH-specific antibodies. We found no HADH in amyloid plaques or vascular amyloid. The neuronal expression of HADH was not correlated with the severity of amyloid load in neuropil. HADH was expressed in vascular smooth muscle cells in young and old controls and in amyloid-free blood vessels in AD cases, but little or no HADH was in smooth muscle cells in arteries with amyloid deposits. The putative intracellular interaction between HADH and Aβ in amyloid-producing cells was further studied in vascular smooth muscle cells isolated from brain blood vessels with amyloid-β angiopathy - the cells that were shown previously to accumulate Aβ intracellularly ['Research advances in Alzheimer's disease and related disorders' (1995) 747; Brain Res. 676 (1995) 225; Neurosci. Lett. 183 (1995) 120]. HADH had a mitochondrial localization and did not co-localize with an endoplasmic reticulum marker. Cells that accumulated Aβ were those with low expression of HADH and the proteins did not co-localize. Explanation of the association between low levels of HADH and deposition of Aβ by brain smooth muscle cells requires further studies.

Original languageEnglish (US)
Pages (from-to)44-53
Number of pages10
JournalBrain Research
Volume907
Issue number1-2
DOIs
StatePublished - Jul 13 2001

Keywords

  • Alzheimer's disease
  • Aβ-blinding protien
  • Cell culture
  • ERAB
  • L-3-hydroxyacyl-coenzyme A dehydrogenase
  • Smooth muscle cells
  • Vascular amyloidosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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