自身抗体谱匹配阿尔茨海默式症和遗忘型轻度认知功能损害患者的脑脊髓液和血清：潜在的致病作用和链接氧化损伤

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 and Alessandra Giorgi, D. Allan Butterfield, Jose Vina and Marzia Perluigi

Affiliation:

关键词: 自身抗体，自身免疫性疾病，阿尔茨海默病，脑脊髓液，免疫蛋白质组学，轻度认知障碍。

摘要: 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.

Cite this article as:

Fabio Di Domenico, Gilda Pupo, Esther Giraldo, Ana Lloret, Mari-Carmen Badia, Maria Eugenia Schinina and Alessandra Giorgi, D. Allan Butterfield, Jose Vina and Marzia Perluigi , Autoantibodies Profile in Matching CSF and Serum from AD and aMCI patients: Potential Pathogenic Role and Link to Oxidative Damage, Current Alzheimer Research 2016; 13 (2) . https://dx.doi.org/10.2174/1567205013666151218131424