title: Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer's disease neurodegeneration.
abstract: Alzheimer's disease (AD) is the most common form of dementia in the elderly. The vast majority of cases are not linked to a known genetic defect and the molecular mechanisms underlying AD pathogenesis are still elusive. Evidence suggests that mitochondrial dysfunction is a prominent feature of the disease, and that mitochondrial DNA (mtDNA) alterations may represent a possible starting point of the pathophysiological cascade. Although specific mtDNA alterations have been reported in AD patients both in brain and peripheral tissues, such as D-loop mutations, 4977-bp deletion and poly-C tract D310 cytosine insertion, a generalized subtle allelic shift has also been demonstrated. This shift is significant for a few nucleotide positions (nps), but it is also detectable for most nps, although at a lower level. As single allelic substitutions can unlikely be determinant, it is proposed that the combination of all of them could lead to a less efficient oxidative phosphorylation, thus influencing AD development and course.
authors.affiliation: Center for Neurobiology of Aging, INRCA IRCCS Ancona, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Casoli
authors.affiliation: Center of Biostatistics, INRCA IRCCS Ancona, Italy.
authors.forename: Liana
authors.initials: L
authors.lastname: Spazzafumo
authors.affiliation: Center for Neurobiology of Aging, INRCA IRCCS Ancona, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Stefano
authors.affiliation: Center for Neurobiology of Aging, INRCA IRCCS Ancona, Italy ; Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche Ancona, Italy.
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Conti
keywords: Alzheimer’s disease; MitoChip; aging; allele; heteroplasmy; mtDNA; mutation