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P2‐243: THE BLOOD PROFILE OF MTDNA ENCODED GENES EXPRESSION IN PARKINSON'S DISEASE PATIENTS AND HEALTHY INDIVIDUALS
Author(s) -
Gezen-Ak Duygu,
Genç Gençer,
Alaylıoğlu Merve,
Sengul Busra,
Kochan Esra,
Atasoy Irem L.,
Kaya Gulec Zeynep E.,
Apaydın Hulya,
Keskin Ebru,
Ertan Sibel,
Dursun Erdinc
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.930
Subject(s) - mitochondrial dna , parkinson's disease , disease , gene , mitochondrion , biology , messenger rna , genetics , medicine , pathology
0.00001), 24(s)-hydroxycholesterol (1.27, 1.03-1.57, p1⁄40.02), SAP (1.30, 1.01-1.67, p1⁄40.05), SAM (0.90, 0.83-0.98, p1⁄40.01), 5-MTHF (0.91, 0.85-0.97, p1⁄40.008), and homocysteine: (plasma 1.19, 95% CI 1.11-1.28, p< 0.00001; CSF 1.15, 95% CI 1.101.34 p1⁄40.06). Conclusions: The neurovascular hypothesis implicates glial, vascular, and neuronal changes in AD pathology. Glial involvement was suggested by highly significant elevations of glial markers YKL-40 and MCP-1. Vascular (endothelial) dysfunction is not implicated as homocysteine was significantly elevated in blood, but NOT CSF. Vascular involvement via reduced cholesterol clearance is suggested by elevation of CSF 24(s)-hydroxycholesterol levels. Additional data analysis yielded unforeseen results, such as possible dysfunction of methylation reactions in the AD brain (SAM, 5MTHF). Our meta-analysis validates glial involvement in the neurovascular hypothesis, suggest that homocysteine lowering therapies may be ineffective, and compels the investigation of further therapeutic targets.