Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Proteome Profile of Olfactory Ecto-Mesenchymal Stem Cells-Derived from Patients with Familial Alzheimer’s Disease Reveals New Insights for AD Study

Version 1 : Received: 11 July 2023 / Approved: 12 July 2023 / Online: 12 July 2023 (13:37:00 CEST)

A peer-reviewed article of this Preprint also exists.

Rochín-Hernández, L.J.; Jiménez-Acosta, M.A.; Ramírez-Reyes, L.; Figueroa-Corona, M.P.; Sánchez-González, V.J.; Orozco-Barajas, M.; Meraz-Ríos, M.A. The Proteome Profile of Olfactory Ecto-Mesenchymal Stem Cells-Derived from Patients with Familial Alzheimer’s Disease Reveals New Insights for AD Study. Int. J. Mol. Sci. 2023, 24, 12606. Rochín-Hernández, L.J.; Jiménez-Acosta, M.A.; Ramírez-Reyes, L.; Figueroa-Corona, M.P.; Sánchez-González, V.J.; Orozco-Barajas, M.; Meraz-Ríos, M.A. The Proteome Profile of Olfactory Ecto-Mesenchymal Stem Cells-Derived from Patients with Familial Alzheimer’s Disease Reveals New Insights for AD Study. Int. J. Mol. Sci. 2023, 24, 12606.

Abstract

Alzheimer's disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment yet, and AD's pathological mechanisms are not yet fully understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer's Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second the Carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in pre-symptoms stages. Finally, we analyzed the differential expressed proteins (DEPs) for biological and functional enrichment. These proteins showed an impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways resembling previous AD reports. Our study is the first proteomic analysis in MSCs from FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies.

Keywords

Proteome; Alzheimer's Disease; Familial Alzheimer's disease; PSEN1; A431E; Mesenchymal Stem Cells; Proteostasis; Olfactory; Neurodegeneration; FAD

Subject

Biology and Life Sciences, Neuroscience and Neurology

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