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

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 thei...

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Bibliographic Details
Published in:Neurobiology of aging 2012-04, Vol.33 (4), p.753-766
Main Authors: Vacirca, D, Delunardo, F, Matarrese, P, Colasanti, T, Margutti, P, Siracusano, A, Pontecorvo, S, Capozzi, A, Sorice, M, Francia, A, Malorni, W, Ortona, E
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Adenosine Triphosphate - pharmacology
Adenosine triphosphate synthase β subunit
Adult
Aged
Aged, 80 and over
Alzheimer Disease - blood
Alzheimer Disease - cerebrospinal fluid
Alzheimer Disease - immunology
Alzheimer's disease
Animals
Annexin A5 - metabolism
Apoptosis
Apoptosis - drug effects
Autoantibodies
Autoantibodies - blood
Autoantibodies - pharmacology
Brain - metabolism
Cell Line, Tumor
Diagnosis
Electrophoresis, Gel, Two-Dimensional
Enzyme-Linked Immunosorbent Assay
Female
Humans
Internal Medicine
Lupus Erythematosus, Systemic - blood
Male
Membrane Potential, Mitochondrial - drug effects
Mice
Middle Aged
Mitochondria
Mitochondrial Proton-Translocating ATPases - immunology
Multiple Sclerosis - blood
Neuroblastoma - pathology
Neurology
Pathogenesis
Sequence Alignment
Time Factors
Young Adult
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Summary: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.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2010.05.013