Journal
ALZHEIMERS & DEMENTIA
Volume 19, Issue 7, Pages 2816-2830Publisher
WILEY
DOI: 10.1002/alz.12868
Keywords
Alzheimer's disease; cerebrospinal fluid; cognition; contactin 5; positron emission tomography; scans; synaptic markers; tau pathology
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This study investigates the role of the CNTN5 rs1461684 G variant and contactin 5 protein in sporadic Alzheimer's disease (sAD). The findings show that CSF contactin 5 levels increase in cognitively unimpaired individuals but decrease in mild cognitive impairment and sAD. CSF contactin 5 is correlated with sAD biomarkers and synaptic markers. The rs1461684 G variant is associated with faster disease progression in cognitively unimpaired subjects. Decreased CNTN5 mRNA levels are observed in the presence of the G allele and as a function of Alzheimer's disease stages. These results highlight the significance of the rs1461684 G variant, contactin 5 protein, and mRNA in the early stages of sAD.
IntroductionWe investigate the CNTN5 rs1461684 G variant and the contactin 5 protein in sporadic Alzheimer's disease (sAD). MethodsContactin 5, sAD biomarkers, and synaptic markers were measured in the cerebrospinal fluid (CSF). Amyloid and tau deposition were assessed using positron emission tomography. Contactin 5 protein and mRNA levels were measured in brain tissue. ResultsCSF contactin 5 increases progressively in cognitively unimpaired individuals and is decreased in mild cognitive impairment and sAD. CSF contactin 5 correlates with sAD biomarkers and with synaptic markers. The rs1461684 G variant associates with faster disease progression in cognitively unimpaired subjects. Cortical full-length and isoform 3 CNTN5 mRNAs are decreased in the presence of the G allele and as a function of Consortium to Establish a Registry for Alzheimer's Disease stages. DiscussionThe newly identified rs1461684 G variant associates with sAD risk, rate of disease progression, and gene expression. Contactin 5 protein and mRNA are affected particularly in the early stages of the disease
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