Autophagy Markers Are Altered in Alzheimer’s Disease, Dementia with Lewy Bodies and Frontotemporal Dementia
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Published:2024-01-17
Issue:2
Volume:25
Page:1125
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Longobardi Antonio1ORCID, Catania Marcella2ORCID, Geviti Andrea3ORCID, Salvi Erika45, Vecchi Elena Rita2, Bellini Sonia1ORCID, Saraceno Claudia1ORCID, Nicsanu Roland1ORCID, Squitti Rosanna16ORCID, Binetti Giuliano7, Di Fede Giuseppe2ORCID, Ghidoni Roberta1ORCID
Affiliation:
1. Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy 2. Neurology 5/Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy 3. Service of Statistics, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy 4. Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy 5. Data Science Center, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy 6. Dipartimento di Scienze di Laboratorio, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy 7. MAC-Memory Clinic and Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy
Abstract
The accumulation of protein aggregates defines distinct, yet overlapping pathologies such as Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). In this study, we investigated ATG5, UBQLN2, ULK1, and LC3 concentrations in 66 brain specimens and 120 plasma samples from AD, DLB, FTD, and control subjects (CTRL). Protein concentration was measured with ELISA kits in temporal, frontal, and occipital cortex specimens of 32 AD, 10 DLB, 10 FTD, and 14 CTRL, and in plasma samples of 30 AD, 30 DLB, 30 FTD, and 30 CTRL. We found alterations in ATG5, UBQLN2, ULK1, and LC3 levels in patients; ATG5 and UBQLN2 levels were decreased in both brain specimens and plasma samples of patients compared to those of the CTRL, while LC3 levels were increased in the frontal cortex of DLB and FTD patients. In this study, we demonstrate alterations in different steps related to ATG5, UBQLN2, and LC3 autophagy pathways in DLB and FTD patients. Molecular alterations in the autophagic processes could play a role in a shared pathway involved in the pathogenesis of neurodegeneration, supporting the hypothesis of a common molecular mechanism underlying major neurodegenerative dementias and suggesting different potential therapeutic targets in the autophagy pathway for these disorders.
Funder
This research was funded under the aegis of the JPND-NIH cooperation programme-2018 and by the Italian Ministry of Health, Italy
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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