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Article type: Research Article
Authors: Mukhamedyarov, Marat A.a; 1 | Rizvanov, Albert A.b; 1 | Yakupov, Eduard Z.a | Zefirov, Andrey L.a | Kiyasov, Andrey P.b | Reis, Helton J.c | Teixeira, Antônio L.c | Vieira, Luciene B.c | Lima, Luciana M.d | Salafutdinov, Ilnur I.b | Petukhova, Elena O.a | Khaiboullina, Svetlana F.b; f | Schlauch, Karen A.e | Lombardi, Vincent C.e; f | Palotás, Andrásb; g; *
Affiliations: [a] Kazan State Medical University, Kazan, Russia | [b] Kazan Federal University, Kazan, Russia | [c] Universidade Federal de Minas Gerais, Belo Horizonte, Brazil | [d] Universidade Federal de Viçosa, Viçosa, Brazil | [e] University of Nevada, Reno, NV, USA | [f] Nevada Center for Biomedical Research, Reno, NV, USA | [g] Asklepios-Med (private medical practice and research center), Szeged, Hungary
Correspondence: [*] Correspondence to: András Palotás, MD, PhD, Asklepios-Med, Kossuth Lajos sgt. 23, H-6722 Szeged, Hungary. Tel.: +36 30 255 6225; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Abstract: Alzheimer’s disease (AD) is a devastating and progressive form of dementia that is typically associated with a build-up of amyloid-β plaques and hyperphosphorylated and misfolded tau protein in the brain. Presently, there is no single test that confirms AD; therefore, a definitive diagnosis is only made after a comprehensive medical evaluation, which includes medical history, cognitive tests, and a neurological examination and/or brain imaging. Additionally, the protracted prodromal phase of the disease makes selection of control subjects for clinical trials challenging. In this study we have utilized a gene-expression array to screen blood and skin punch biopsy (fibroblasts, keratinocytes, and endothelial cells) for transcriptional differences that may lead to a greater understanding of AD as well as identify potential biomarkers. Our analysis identified 129 differentially expressed genes from blood of dementia cases when compared to healthy individuals, and four differentially expressed punch biopsy genes between AD subjects and controls. Additionally, we identified a set of genes in both tissue compartments that showed transcriptional variation in AD but were largely stable in controls. The translational products of these variable genes are involved in the maintenance of the Golgi structure, regulation of lipid metabolism, DNA repair, and chromatin remodeling. Our analysis potentially identifies specific genes in both tissue compartments that may ultimately lead to useful biomarkers and may provide new insight into the pathophysiology of AD.
Keywords: Alzheimer’s disease, amyloid, biomarker, diagnostics, early diagnosis, endothelial cell, fibroblast, inflammation, keratinocyte, lymphocyte, mild cognitive impairment, neurodegeneration, oxidative stress, skin biopsy
DOI: 10.3233/JAD-160457
Journal: Journal of Alzheimer's Disease, vol. 54, no. 4, pp. 1373-1383, 2016
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