Autoantibodies to the adenosine triphosphate synthase play a pathogenetic role in Alzheimer's disease.
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.
Vacirca
D
D
Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy.
Delunardo
F
F
Matarrese
P
P
Colasanti
T
T
Margutti
P
P
Siracusano
A
A
Pontecorvo
S
S
Capozzi
A
A
Sorice
M
M
Francia
A
A
Malorni
W
W
Ortona
E
E
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid / Q000276:immunology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001323:Autoantibodies / Q000097:blood* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008875:Middle Aged; D025261:Mitochondrial Proton-Translocating ATPases / Q000276:immunology*; D009103:Multiple Sclerosis / Q000097:blood; D009447:Neuroblastoma / Q000473:pathology; D016415:Sequence Alignment; D013997:Time Factors; D055815:Young Adult
C506526:ATP5F1B protein, human; D017304:Annexin A5; D001323:Autoantibodies; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases