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Detection of Alzheimer’s Disease at Mild Cognitive Impairment and Disease Progression Using Autoantibodies as Blood-based Biomarkers

ABSTRACT: Human serum samples from Alzheimer's disease driven mild cognitive impairment and non-diseased controls were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. Other neurodegenerative and non-neurodegenerative diseases were also used to help measure the specificity of the selected biomarkers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE74763 | GEO | 2016/05/03

SECONDARY ACCESSION(S): PRJNA301443

REPOSITORIES: GEO

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Project description:BackgroundDementia is a debilitating neurological disease affecting millions of people worldwide. The exact mechanisms underlying the initiation and progression of the disease remain to be fully defined. There is an increasing body of evidence for the role of immune dysregulation in the pathogenesis of dementia, where blood-borne autoimmune antibodies have been studied as potential markers associated with pathological mechanisms of dementia.MethodsThis study included plasma from 50 cognitively normal individuals, 55 subjects with MCI (mild cognitive impairment), and 22 subjects with dementia. Autoantibody profiling for more than 1,600 antigens was performed using a high throughput microarray platform to identify differentially expressed autoantibodies in MCI and dementia.ResultsThe differential expression analysis identified 33 significantly altered autoantibodies in the plasma of patients with dementia compared to cognitively normal subjects, and 38 significantly altered autoantibodies in the plasma of patients with dementia compared to subjects with MCI. And 20 proteins had significantly altered autoantibody responses in MCI compared to cognitively normal individuals. Five autoantibodies were commonly dysregulated in both dementia and MCI, including anti-CAMK2A, CKS1B, ETS2, MAP4, and NUDT2. Plasma levels of anti-ODF3, E6, S100P, and ARHGDIG correlated negatively with the cognitive performance scores (MoCA) (r2 -0.56 to -0.42, value of p < 0.001). Additionally, several proteins targeted by autoantibodies dysregulated in dementia were significantly enriched in the neurotrophin signaling pathway, axon guidance, cholinergic synapse, long-term potentiation, apoptosis, glycolysis and gluconeogenesis.ConclusionWe have shown multiple dysregulated autoantibodies in the plasma of subjects with MCI and dementia. The corresponding proteins for these autoantibodies are involved in neurodegenerative pathways, suggesting a potential impact of autoimmunity on the etiology of dementia and the possible benefit for future therapeutic approaches. Further investigations are warranted to validate our findings.

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Detection of Alzheimer’s Disease at Mild Cognitive Impairment and Disease Progression Using Autoantibodies as Blood-based Biomarkers

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