The reduction of NADH Ubiquinone oxidoreductase 24-and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer's disease

NADH: ubiquinone oxidoreductase (complex I), one of the most complicated mu lti-protein enzyme complexes, is important for energy metabolism because it is the initial enzyme of the mitochondrial respiratory chain. Deficiency o f complex I is frequently found in various tissues of patients with neurode generative disease. Here we studied the protein levels of complex I 24- and 75-kDa subunits in several brain regions from patients with Down syndrome (DS) and Alzheimer's disease (AD). We determined protein levels of complex I 24-, 75-kDa subunits and mitochondrial marker proteins mitochondrial matr ix protein P1 (hsp60) and aconitate hydratase from seven brain regions of p atients with DS, AD and controls. Proteins were separated by two-dimensiona l (2-D) gel electrophoresis and identified by matrix-assisted laser desorpt ion ionization mass spectrometry (MALDI-MS). Complex I 24-kDa subunit was s ignificantly reduced in occipital cortex and thalamus in patients with DS a nd temporal and occipital cortices in patients with AD. Complex I 75-kDa su bunit was significantly reduced in brain regions from patients with DS (tem poral, occipital and caudate nucleus) and AD (parietal cortex). Reductions of two subunits of complex I may lead to the impairment of energy metabolis m and result in neuronal cell death (apoptosis), a hallmark of both neurode generative disorders. (C) 2001 Elsevier Science Inc. All rights reserved.