Mitochondrial alterations in fibroblasts from sporadic Alzheimer's disease (AD) patients correlate with AD-related clinical hallmarks.

Autor: Eysert F; INSERM, CNRS, Institute of Molecular and Cellular Pharmacology, Laboratory of Excellence DistALZ, Université Côte d'Azur, 660 Route des Lucioles, 06560, Sophia-Antipolis, Valbonne, France., Kinoshita PF; INSERM, CNRS, Institute of Molecular and Cellular Pharmacology, Laboratory of Excellence DistALZ, Université Côte d'Azur, 660 Route des Lucioles, 06560, Sophia-Antipolis, Valbonne, France., Lagarde J; Department of Neurology of Memory and Language, GHU Paris Psychiatrie & Neurosciences, Hôpital Sainte Anne, 75014, Paris, France.; Université Paris-Cité, 75006, Paris, France.; BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, Inserm, Université Paris-Saclay, 91401, Orsay, France., Lacas-Gervais S; Centre Commun de Microscopie Appliquée, Université de Nice Côte d'Azur, 06108, Nice, France., Xicota L; UPMC University Paris 06, UMRS 1127, Sorbonne Universités, Paris, France.; ICM Research Center, CNRS UMR 7225, Paris, France., Dorothée G; Inserm, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-Antoine, Sorbonne Université, 75012, Paris, France., Bottlaender M; BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, Inserm, Université Paris-Saclay, 91401, Orsay, France.; UNIACT, Neurospin, Joliot Institute, CEA, Université Paris-Saclay, 91140, Gif sur Yvette, France., Checler F; INSERM, CNRS, Institute of Molecular and Cellular Pharmacology, Laboratory of Excellence DistALZ, Université Côte d'Azur, 660 Route des Lucioles, 06560, Sophia-Antipolis, Valbonne, France., Potier MC; UPMC University Paris 06, UMRS 1127, Sorbonne Universités, Paris, France.; ICM Research Center, CNRS UMR 7225, Paris, France., Sarazin M; Department of Neurology of Memory and Language, GHU Paris Psychiatrie & Neurosciences, Hôpital Sainte Anne, 75014, Paris, France.; Université Paris-Cité, 75006, Paris, France.; BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, Inserm, Université Paris-Saclay, 91401, Orsay, France., Chami M; INSERM, CNRS, Institute of Molecular and Cellular Pharmacology, Laboratory of Excellence DistALZ, Université Côte d'Azur, 660 Route des Lucioles, 06560, Sophia-Antipolis, Valbonne, France. mchami@ipmc.cnrs.fr.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2024 Jun 08; Vol. 12 (1), pp. 90. Date of Electronic Publication: 2024 Jun 08.
DOI: 10.1186/s40478-024-01807-x
Abstrakt: Mitochondrial dysfunctions are key features of Alzheimer's disease (AD). The occurrence of these disturbances in the peripheral cells of AD patients and their potential correlation with disease progression are underinvestigated. We studied mitochondrial structure, function and mitophagy in fibroblasts from healthy volunteers and AD patients at the prodromal (AD-MCI) or demented (AD-D) stages. We carried out correlation studies with clinical cognitive scores, namely, (i) Mini-Mental State Examination (MMSE) and (ii) Dementia Rating-Scale Sum of Boxes (CDR-SOB), and with (iii) amyloid beta (Aβ) plaque burden (PiB-PET imaging) and (iv) the accumulation of peripheral amyloid precursor protein C-terminal fragments (APP-CTFs). We revealed alterations in mitochondrial structure as well as specific mitochondrial dysfunction signatures in AD-MCI and AD-D fibroblasts and revealed that defective mitophagy and autophagy are linked to impaired lysosomal activity in AD-D fibroblasts. We reported significant correlations of a subset of these dysfunctions with cognitive decline, AD-related clinical hallmarks and peripheral APP-CTFs accumulation. This study emphasizes the potential use of peripheral cells for investigating AD pathophysiology.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje