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Mitochondrial DNA 4977 bp deletion and OH⁸dG levels correlate in the brain of aged subjects but not Alzheimer's disease patients

ANGELA MARIA SERENA LEZZA^*, PATRIZIA MECOCCI, ANTONELLA CORMIO^*, M. FLINT BEAL, ANTONIO CHERUBINI, PALMIRO CANTATORE^*, UMBERTO SENIN and MARIA NICOLA GADALETA^*1

^* Department of Biochemistry and Molecular Biology, University of Bari, 70125 Bari, Italy;
Department of Gerontology and Geriatrics, University of Perugia, 06122 Perugia, Italy; and
Neurology Research, MGH Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

¹Correspondence: Department of Biochemistry and Molecular Biology, University of Bari, Via Orabona 4, 70125 Bari, Italy. E-mail: m.n.gadaleta{at}biologia.uniba.it

The levels of mitochondrial DNA 4977 bp deletion (mtDNA⁴⁹⁷⁷) and mitochondrial DNA 8'-hydroxy-2'-deoxyguanosine (OH⁸dG) were determined in the same samples from two brain areas of healthy subjects and Alzheimer's disease (AD) patients. A positive correlation between the age-related increases of mtDNA⁴⁹⁷⁷ and of OH⁸dG levels was found in the brain of healthy individuals. On the contrary, in both brain areas of AD patients, mtDNA⁴⁹⁷⁷ levels were very low in the presence of high OH⁸dG amounts. These results might be explained assuming that the increase of OH⁸dG above a threshold level, as in AD patients, implies consequences for mtDNA replication and neuronal cell survival.—Lezza, A. M. S., Mecocci, P., Cormio, A., Beal, M. F., Cherubini, A., Cantatore, P., Senin, U., Gadaleta, M. N. Mitochondrial DNA 4977 bp deletion and OH⁸dG levels correlate in the brain of aged subjects but not Alzheimer's disease patients.

Key Words: aging • mtDNA deletions • mtDNA oxidative damage • neurodegenerative disease

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