title: Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer's Disease.
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.
authors: Kazan State Medical University, Kazan, Russia.
authors: Marat A
authors: MA
authors: Mukhamedyarov
authors: Kazan Federal University, Kazan, Russia.
authors: Albert A
authors: AA
authors: Rizvanov
authors: Kazan State Medical University, Kazan, Russia.
authors: Eduard Z
authors: EZ
authors: Yakupov
authors: Kazan State Medical University, Kazan, Russia.
authors: Andrey L
authors: AL
authors: Zefirov
authors: Kazan Federal University, Kazan, Russia.
authors: Andrey P
authors: AP
authors: Kiyasov
authors: Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Helton J
authors: HJ
authors: Reis
authors: Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Antônio L
authors: AL
authors: Teixeira
authors: Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors: Luciene B
authors: LB
authors: Vieira
authors: Universidade Federal de Viçosa, Viçosa, Brazil.
authors: Luciana M
authors: LM
authors: Lima
authors: Kazan Federal University, Kazan, Russia.
authors: Ilnur I
authors: II
authors: Salafutdinov
authors: Kazan State Medical University, Kazan, Russia.
authors: Elena O
authors: EO
authors: Petukhova
authors: Kazan Federal University, Kazan, Russia.|Nevada Center for Biomedical Research, Reno, NV, USA.
authors: Svetlana F
authors: SF
authors: Khaiboullina
authors: University of Nevada, Reno, NV, USA.
authors: Karen A
authors: KA
authors: Schlauch
authors: University of Nevada, Reno, NV, USA.|Nevada Center for Biomedical Research, Reno, NV, USA.
authors: Vincent C
authors: VC
authors: Lombardi
authors: Kazan Federal University, Kazan, Russia.|Asklepios-Med (private medical practice and research center), Szeged, Hungary.
authors: András
authors: A
authors: Palotás
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D010865:Pilot Projects; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D015415:Biomarkers
keywords: Alzheimer’s disease; amyloid; biomarker; diagnostics; early diagnosis; endothelial cell; fibroblast; inflammation; keratinocyte; lymphocyte; mild cognitive impairment; neurodegeneration; oxidative stress; skin biopsy