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

Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy.
Neurobiology of aging (Impact Factor: 4.85). 04/2012; 33(4):753-66. DOI: 10.1016/j.neurobiolaging.2010.05.013
Source: PubMed

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.

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Available from: Maurizio Sorice, Nov 17, 2014
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    • "In method B (Harris et al. 2005) plasma membranes, collapsed over the nuclei, were separated as floating membranes by isopycnic centrifugation using 2 M sucrose (PMB). Considering that the ectopic enzyme is mainly localized in lipid rafts composed of cholesterol and sphingolipids (Gorai et al. 2012; Vacirca et al. 2012), both plasma membrane preparations were treated with the mild non-ionic detergent digitonin (Nielsen et al. 2005), which forms an equimolar complex with cholesterol. Moreover, digitonin was chosen being widely used to extract F 0 F 1 complexes from the inner mitochondrial membrane (Wittig et al. 2006), because it maintains the ATP synthase oligomeric forms (Giorgio et al. 2009). "
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