DEF8 and Autophagy-Associated Genes Are Altered in Mild Cognitive Impairment, Probable Alzheimer’s Disease Patients, and a Transgenic Model of the Disease
| Autor: | Patricio Manque, Nohela B Arévalo, Maria I. Behrens, Ute Woehlbier, Carol D. SanMartín, Esteban Leyton, Paola Murgas, Claudia Duran-Aniotz, Bastián I Cortés, Sandra Espinoza, Wileidy Gomez, Diego Matus, José Matías Benitez, Melissa Nassif, Claudio Hetz |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Mice Transgenic Immunofluorescence Peripheral blood mononuclear cell Flow cytometry Mice 03 medical and health sciences 0302 clinical medicine Western blot Alzheimer Disease Lysosome Gene expression Autophagy Animals Humans Medicine Cognitive Dysfunction Aged Aged 80 and over medicine.diagnostic_test business.industry General Neuroscience Intracellular Signaling Peptides and Proteins Brain General Medicine Middle Aged Pathophysiology Psychiatry and Mental health Clinical Psychology 030104 developmental biology medicine.anatomical_structure Immunology Female Geriatrics and Gerontology business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 82:S163-S178 |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Background: Disturbances in the autophagy/endolysosomal systems are proposed as early signatures of Alzheimer’s disease (AD). However, few studies are available concerning autophagy gene expression in AD patients. Objective: To explore the differential expression of classical genes involved in the autophagy pathway, among them a less characterized one, DEF8 (Differentially expressed in FDCP 8), initially considered a Rubicon family member, in peripheral blood mononuclear cells (PBMCs) from individuals with mild cognitive impairment (MCI) and probable AD (pAD) and correlate the results with the expression of DEF8 in the brain of 5xFAD mice. Method: By real-time PCR and flow cytometry, we evaluated autophagy genes levels in PBMCs from MCI and pAD patients. We evaluated DEF8 levels and its localization in brain samples of the 5xFAD mice by real-time PCR, western blot, and immunofluorescence. Results: Transcriptional levels of DEF8 were significantly reduced in PBMCs of MCI and pAD patients compared with healthy donors, correlating with the MoCA and MoCA-MIS cognitive tests scores. DEF8 protein levels were increased in lymphocytes from MCI but not pAD, compared to controls. In the case of brain samples from 5xFAD mice, we observed a reduced mRNA expression and augmented protein levels in 5xFAD compared to age-matched wild-type mice. DEF8 presented a neuronal localization. Conclusion: DEF8, a protein proposed to act at the final step of the autophagy/endolysosomal pathway, is differentially expressed in PBMCs of MCI and pAD and neurons of 5xFAD mice. These results suggest a potential role for DEF8 in the pathophysiology of AD. |
| Databáze: | OpenAIRE |
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