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Authors: Petukhova, Elena O. | Mukhamedshina, Yana O. | Salafutdinov, Ilnur I. | Garanina, Ekaterina E. | Kaligin, Maxim S. | Leushina, Alina V. | Rizvanov, Albert A. | Reis, Helton J. | Palotás, András | Zefirov, Andrey L. | Mukhamedyarov, Marat A.

Article Type: Research Article

Abstract: Background/Objective: Alzheimer’s disease (AD) is a progressive incurable neurodegenerative disorder. Glial cell line-derived neurotrophic factor (GDNF) is a prominent regulator of brain tissue and has an impressive potential for use in AD therapy. While its metabolism is still not fully understood, delivering neuropeptides such as GDNF via umbilical cord blood mononuclear cells (UCBMCs) to the sites of neurodegeneration is a promising approach in the development of innovative therapeutic avenues. Methods: UCBMCs were transduced with adenoviral vectors expressing GDNF and injected into AD transgenic mice. Various parameters including homing and survival of transplanted cells, expression of GDNF and synaptic proteins, as …well as spatial memory were evaluated. Results: UCBMCs were observed in the hippocampus and cortex several weeks after transplantation, and their long-term presence was associated with improved spatial memory. Post-synaptic density protein 95 (PSD-95) and synaptophysin levels in the hippocampus were also effectively restored following the procedure in AD mice. Conclusions: Our data indicate that gene-cell therapy with GDNF-overexpressing UCBMCs may produce long-lasting neuroprotection and stimulation of synaptogenesis. Such adenoviral constructs could potentially possess a high therapeutic potential for the treatment of AD. Show more

Keywords: Alzheimer’s disease, glial cell line-derived neuro-trophic factor, post-synaptic density protein 95, synaptophysin, umbilical cord blood mono-nuclear cells

DOI: 10.3233/JAD-190150

Citation: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 443-453, 2019

Authors: Mukhamedyarov, Marat A. | Rizvanov, Albert A. | Yakupov, Eduard Z. | Zefirov, Andrey L. | Kiyasov, Andrey P. | Reis, Helton J. | Teixeira, Antônio L. | Vieira, Luciene B. | Lima, Luciana M. | Salafutdinov, Ilnur I. | Petukhova, Elena O. | Khaiboullina, Svetlana F. | Schlauch, Karen A. | Lombardi, Vincent C. | Palotás, András

Article Type: Research Article

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. Show more

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

Citation: Journal of Alzheimer's Disease, vol. 54, no. 4, pp. 1373-1383, 2016