Anti-ATP Synthase Autoantibodies from Patients with Alzheimer's Disease Reduce Extracellular HDL Level

Article type: Research Article

Authors: Vacirca, Davide^a | Barbati, Cristiana^{a; b} | Scazzocchio, Beatrice^c | Masella, Roberta^c | Rosano, Giuseppe^b | Malorni, Walter^{b; d; 1} | Ortona, Elena^{a; *; 1}

Affiliations: [a] Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy | [b] Istituto San Raffaele Dulmoisa, Sulmona (AQ), Italy | [c] Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy | [d] Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità Rome, Italy

Correspondence: [*] Correspondence to: Dr. Elena Ortona, Department of Cell Biology and Neuroscienes, Istituto Superiore di Sanità, Rome, Italy. Tel.: +390649902753; Fax: +390649902040; E-mail: Elena.ortona@iss.it.

Note: [1] Both considered as senior authors.

Abstract: Aside from being an integral protein involved in the synthesis and hydrolysis of ATP, Ecto-F1-ATPase plays a role in cholesterol homeostasis. We demonstrated the presence of autoantibodies to ecto-F1-ATPase (ASabs) in sera and cerebrospinal fluids from patients with Alzheimer's disease (AD). Herein we show that ASabs, unlike irrelevant antibodies, can increase cellular uptake of HDL, a risk factor for the development of AD, via a mechanism involving the prototypical function of ecto-F1-ATPase: the generation of ADP due to the hydrolysis of ATP. Piceatannol, a specific inhibitor ecto-F1-ATPase, completely hindered these effects. We hypothesize that ASabs could exert a pathogenetic role in AD.

Keywords: Alzheimer's disease, ATP synthase, autoantibodies, HDL, piceatannol

DOI: 10.3233/JAD-2011-110350

Journal: Journal of Alzheimer's Disease, vol. 26, no. 3, pp. 441-445, 2011