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

L-3-hydroxyacyl-coenzyme A dehydrogenase type II (HADH) was described as an endoplasmic reticulum amyloid beta -peptide-binding protein (ERAB), which enhances A beta toxicity, and accumulates in neurons in Alzheimer's disease (AD). Hence, HADH/ERAB was suggested to mediate the amyloid-induced neurod egeneration. We estimated the in vivo interactions of HADH and A beta in an immunocytochemical study of ten Alzheimer's disease and seven normal brain s using five monoclonal HADH-specific antibodies. We found no HADH in amylo id plaques or vascular amyloid. The neuronal expression of HADH was not cor related with the severity of amyloid load in neuropil. HADH was expressed i n vascular smooth muscle cells in young and old controls and in amyloid-fre e blood vessels in AD cases, but little or no HADH was in smooth muscle cel ls in arteries with amyloid deposits. The putative intracellular interactio n between HADH and A beta in amyloid-producing cells was further studied in vascular smooth muscle cells isolated from brain blood vessels with amyloi d-beta angiopathy-the cells that were shown previously to accumulate A beta intracellularly ['Research advances in Alzheimer's disease and related dis orders' (1995) 747: Brain Res. 676 (1995) 225: Neurosci. Lett. 183 (1995) 1 20]. HADH had a mitochondrial localization and did not co-localize with an endoplasmic reticulum marker. Cells that accumulated A beta were those with low expression of HADH and the proteins did not co-localize. Explanation o f the association between low levels of HADH and deposition of A beta by br ain smooth muscle cells requires further studies. (C) 2001 Elsevier Science B.V. All rights reserved.