Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation

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The use of quantitative endophenotypes from cerebrospinal fluid has led to the identification of several genetic variants that alter risk or rate of progression of Alzheimer's disease. Here we have analyzed the levels of 58 disease-related proteins in the cerebrospinal fluid for association with millions of variants across the human genome. We have identified significant, replicable associations with 5 analytes, Angiotensin-converting enzyme, Chemokine (C-C motif) ligand 2, Chemokine (C-C motif) ligand 4, Interleukin 6 receptor and Matrix metalloproteinase-3. Our results suggest that these variants play a regulatory role in the respective protein levels and are relevant to the inflammatory and amyloid processing pathways. Variants in associated with ACE and those associated with MMP3 levels also show association with risk for Alzheimer's disease in the expected directions. These associations are consistent in cerebrospinal fluid and plasma and in samples with only cognitively normal individuals suggesting that they are relevant in the regulation of these protein levels beyond the context of Alzheimer's disease.

Vyšlo v časopise: Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004758
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004758

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