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A combination of multiple autoantibodies is associated with the risk of Alzheimer's disease and cognitive impairment.

ABSTRACT: Autoantibodies are self-antigen reactive antibodies that play diverse roles in the normal immune system, tissue homeostasis, and autoimmune and neurodegenerative diseases. Anti-neuronal autoantibodies have been detected in neurodegenerative disease serum, with unclear significance. To identify diagnostic biomarkers of Alzheimer's disease (AD), we analyzed serum autoantibody profiles of the HuProt proteome microarray using the discovery set of cognitively normal control (NC, n = 5) and AD (n = 5) subjects. Approximately 1.5-fold higher numbers of autoantibodies were detected in the AD group (98.0 ± 39.9/person) than the NC group (66.0 ± 39.6/person). Of the autoantigen candidates detected in the HuProt microarray, five autoantigens were finally selected for the ELISA-based validation experiment using the validation set including age- and gender-matched normal (NC, n = 44), mild cognitive impairment (MCI, n = 44) and AD (n = 44) subjects. The serum levels of four autoantibodies including anti-ATCAY, HIST1H3F, NME7 and PAIP2 IgG were significantly different among NC, MCI and/or AD groups. Specifically, the anti-ATCAY autoantibody level was significantly higher in the AD (p = 0.003) and MCI (p = 0.015) groups compared to the NC group. The anti-ATCAY autoantibody level was also significantly correlated with neuropsychological scores of MMSE (r_s = - 0.229, p = 0.012), K-MoCA (r_s = - 0.270, p = 0.003), and CDR scores (r_s = 0.218, p = 0.016). In addition, a single or combined occurrence frequency of anti-ATCAY and anti-PAIP2 autoantibodies was significantly associated with the risk of MCI and AD. This study indicates that anti-ATCAY and anti-PAIP2 autoantibodies could be a potential diagnostic biomarker of AD.

SUBMITTER: Shim SM

PROVIDER: S-EPMC8789802 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCancer-related cognitive impairment is an important complication in cancer patients, yet the underlying mechanisms remain unknown. Over the last decade, the field of paraneoplastic neurological syndromes has been dramatically changed by the discovery of new neuronal autoantibodies, some of them associated with cognitive impairment. We aimed to assess the prevalence of neuronal autoantibodies in melanoma patients and their association with neurological and cognitive dysfunction.Patients and methodsA total of 157 consecutive melanoma patients with a median age of 63 years were recruited at the Department of Dermatology, Charité-Universitätsmedizin Berlin and tested for neuronal autoantibodies. A comprehensive neuropsychological assessment was carried out in a selected subgroup of 84 patients after exclusion of patients with confounding factors for a cognitive dysfunction, including brain metastases, relevant medication, and neurological disorders.ResultsNeuronal autoantibodies were found in 22.3% of melanoma patients. The most frequent antibodies were IgA/IgM anti-NMDAR antibodies. Applying the International Cognition and Cancer Task Force criteria, 36.9% had cognitive impairment, however, with a threefold higher odds in antibody-positive compared with antibody-negative patients (57.1% versus 30.2%, OR = 3.1, 95% CI: 1.1 to 8.6; P = 0.037). In patients with anti-NMDAR antibodies, this impairment increased with higher antibody titers (P = 0.007). Antibody-positive patients had a significantly impaired overall cognitive performance (z-value: -0.38 ± 0.69 versus 0.00 ± 0.56; P = 0.014) as well as significant impairments in tests of memory, attention, and executive function. In a multiple linear regression analysis, autoantibodies were an independent risk factor for cognitive impairment (B = -0.282; 95% CI: -0.492 to -0.071; P = 0.009). Autoantibody seropositivity was associated with immune checkpoint inhibitor treatment and a history of autoimmune diseases.ConclusionsA large number of melanoma patients harbor neuronal autoantibodies that are associated with significant cognitive impairment affecting memory, attention, and executive function. Neuronal autoantibodies might represent a pathophysiological factor and possible biomarker in the development of cancer-related cognitive impairment.

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A combination of multiple autoantibodies is associated with the risk of Alzheimer's disease and cognitive impairment.

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