Title:Autoantibodies Profile in Matching CSF and Serum from AD and aMCI patients: Potential Pathogenic Role and Link to Oxidative Damage
Volume: 13
Issue: 2
Author(s): Fabio Di Domenico, Gilda Pupo, Esther Giraldo, Ana Lloret, Mari-Carmen Badia, Maria Eugenia Schinina, Alessandra Giorgi, D. Allan Butterfield, Jose Vina and Marzia Perluigi
Affiliation:
Keywords:
Autoantibodies, autoimmunity, Alzheimer disease, cerebrospinal fluid, immunoproteomics, mild cognitive
impairment.
Abstract: Alzheimer disease (AD) is the most common form of dementia among the elderly and is
characterized by progressive loss of memory and cognition. Amyloid-ß-peptide (Aß) forms senile
plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles, are the hallmarks
of AD neuropathology. Evidence support the involvement of immune system in AD progression and
current concepts regarding its pathogenesis include the participation of inflammatory and autoimmune
components in the neurodegenerative process. Pathologically, immune system components have been detected in the
brain, cerebrospinal fluid (CSF) and in serum of AD subjects and their trend of variation correlates with disease progression.
However, patients with AD present significantly lower levels of antibody immunoreactivity against Aß in serum and
CSF than healthy controls suggesting that a depletion of such patrolling system is involved in the deposition of toxic aggregates
in AD. Within this frame, incomplete and often controversial results are reported about CNS immune/
autoimmune responses during AD, and a better comprehension of such processes is needed. Our research will aim
to shed light on the nature and potential role of autoantibodies in CSF and serum from AD and amnestic mild cognitive
impairment (aMCI) patients compared to healthy subjects by using an immunoproteomics approach. Our method allows
recognition of natural occurring antibodies by the identification of brain antigen targeted by human IgGs. Overall our data
reveal that the alterations of autoantibodies profile both in CSF and serum follow disease staging and progression. However,
we demonstrate a fair overlap between CSF and serum suggesting the existence of different immunogenic events. Interestingly,
CSF autoantibodies recognized, among others, key players of energy metabolic pathway, including glycolysis
and TCA cycle, found oxidatively modified in AD brain studies. These data suggest a potential casual sequence between
oxidative damage at brain level, autoantibodies presence in CSF and reduced energy metabolism of AD patients.
