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