Autoantibodies to the adenosine triphosphate synthase play a pathogenetic role in Alzheimer's disease

D. Vacirca, F. Delunardo, P. Matarrese, T. Colasanti, P. Margutti, A. Siracusano, S. Pontecorvo, A. Capozzi, M. Sorice, A. Francia, W. Malorni, E. Ortona

Research output: Contribution to journalArticlepeer-review

Abstract

It has become evident that an autoimmune component could play a role in Alzheimer's disease (AD) onset and/or progression. The aim of this study was to identify neuronal antigenic targets specifically recognized by serum autoantibodies and to investigate their cellular effects and their possible pathogenetic role. We identified, by an immunoproteomic approach using mouse brain proteins, the adenosine triphosphate (ATP) synthase β subunit as a new autoantigen in AD. Using an ELISA assay we found that serum anti-ATP synthase autoantibodies were present in 38% of patients with AD, but in no age-matched healthy subjects or in patients with Parkinson's disease or atherosclerosis. Analytical cytology studies, using SH-SY5Y neuroblastoma cell line, showed that ATP synthase autoantibodies were capable of inducing the inhibition of ATP synthesis, alterations of mitochondrial homeostasis and cell death by apoptosis. These findings suggest that autoantibodies specific to ATP synthase can exert a pathogenetic role via a mechanism that brings into play the impairment of the extracellular ATP homeostasis and the alteration of mitochondrial function triggering cell death by apoptosis.

Original languageEnglish
Pages (from-to)753-766
Number of pages14
JournalNeurobiology of Aging
Volume33
Issue number4
DOIs
Publication statusPublished - Apr 2012

Keywords

  • Adenosine triphosphate synthase β subunit
  • Alzheimer's disease
  • Apoptosis
  • Autoantibodies
  • Diagnosis
  • Mitochondria
  • Pathogenesis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

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