Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s Disease
Background: Individuals with specific <i>TREM2</i> gene variants that encode for a Triggering Receptor Expressed on Myeloid cells 2 have a higher prevalence of Alzheimer’s disease (AD). By interacting with amyloid and apolipoproteins, the TREM2 receptor regulates the number of myeloid ce...
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MDPI AG
2023-07-01
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| Online Access: | https://www.mdpi.com/2035-8377/15/3/53 |
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| author | Ena Španić Popovački Mirjana Babić Leko Lea Langer Horvat Klara Brgić Željka Vogrinc Marina Boban Nataša Klepac Fran Borovečki Goran Šimić |
| author_facet | Ena Španić Popovački Mirjana Babić Leko Lea Langer Horvat Klara Brgić Željka Vogrinc Marina Boban Nataša Klepac Fran Borovečki Goran Šimić |
| author_sort | Ena Španić Popovački |
| collection | DOAJ |
| description | Background: Individuals with specific <i>TREM2</i> gene variants that encode for a Triggering Receptor Expressed on Myeloid cells 2 have a higher prevalence of Alzheimer’s disease (AD). By interacting with amyloid and apolipoproteins, the TREM2 receptor regulates the number of myeloid cells, phagocytosis, and the inflammatory response. Higher <i>TREM2</i> expression has been suggested to protect against AD. However, it is extremely difficult to comprehend TREM2 signaling in the context of AD. Previous results are variable and show distinct effects on diverse pathological changes in AD, differences between soluble and membrane isoform signaling, and inconsistency between animal models and humans. In addition, the relationship between TREM2 and inflammasome activation pathways is not yet entirely understood. Objective: This study aimed to determine the relationship between soluble TREM2 (sTREM2) levels in cerebrospinal fluid (CSF) and plasma samples and other indicators of AD pathology. Methods: Using the Enzyme-Linked Immunosorbent Assay (ELISA), we analyzed 98 samples of AD plasma, 35 samples of plasma from individuals with mild cognitive impairment (MCI), and 11 samples of plasma from healthy controls (HC), as well as 155 samples of AD CSF, 90 samples of MCI CSF, and 50 samples of HC CSF. Results: CSF sTREM2 levels were significantly correlated with neurofibrillary degeneration, cognitive decline, and inflammasome activity in AD patients. In contrast to plasma sTREM2, CSF sTREM2 levels in the AD group were higher than those in the MCI and HC groups. Moreover, concentrations of sTREM2 in CSF were substantially higher in the MCI group than in the HC group, indicating that CSF sTREM2 levels could be used not only to distinguish between HC and AD patients but also as a biomarker to detect earlier changes in the MCI stage. Conclusions: The results indicate CSF sTREM2 levels reliably predict neurofibrillary degeneration, cognitive decline, and inflammasome activation, and also have a high diagnostic potential for distinguishing diseased from healthy individuals. To add sTREM2 to the list of required AD biomarkers, future studies will need to include a larger number of patients and utilize a standardized methodology. |
| first_indexed | 2024-03-10T22:21:13Z |
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| institution | Directory Open Access Journal |
| issn | 2035-8377 |
| language | English |
| last_indexed | 2024-03-10T22:21:13Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-524abe23403f4537a0329e68888209fd2023-11-19T12:15:44ZengMDPI AGNeurology International2035-83772023-07-0115384285610.3390/neurolint15030053Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s DiseaseEna Španić Popovački0Mirjana Babić Leko1Lea Langer Horvat2Klara Brgić3Željka Vogrinc4Marina Boban5Nataša Klepac6Fran Borovečki7Goran Šimić8Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Šalata 12, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Šalata 12, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Šalata 12, 10000 Zagreb, CroatiaDepartment of Neurosurgery, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, CroatiaLaboratory for Neurobiochemistry, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, CroatiaDepartment of Neurology, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, CroatiaDepartment of Neurology, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, CroatiaDepartment of Neurology, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Šalata 12, 10000 Zagreb, CroatiaBackground: Individuals with specific <i>TREM2</i> gene variants that encode for a Triggering Receptor Expressed on Myeloid cells 2 have a higher prevalence of Alzheimer’s disease (AD). By interacting with amyloid and apolipoproteins, the TREM2 receptor regulates the number of myeloid cells, phagocytosis, and the inflammatory response. Higher <i>TREM2</i> expression has been suggested to protect against AD. However, it is extremely difficult to comprehend TREM2 signaling in the context of AD. Previous results are variable and show distinct effects on diverse pathological changes in AD, differences between soluble and membrane isoform signaling, and inconsistency between animal models and humans. In addition, the relationship between TREM2 and inflammasome activation pathways is not yet entirely understood. Objective: This study aimed to determine the relationship between soluble TREM2 (sTREM2) levels in cerebrospinal fluid (CSF) and plasma samples and other indicators of AD pathology. Methods: Using the Enzyme-Linked Immunosorbent Assay (ELISA), we analyzed 98 samples of AD plasma, 35 samples of plasma from individuals with mild cognitive impairment (MCI), and 11 samples of plasma from healthy controls (HC), as well as 155 samples of AD CSF, 90 samples of MCI CSF, and 50 samples of HC CSF. Results: CSF sTREM2 levels were significantly correlated with neurofibrillary degeneration, cognitive decline, and inflammasome activity in AD patients. In contrast to plasma sTREM2, CSF sTREM2 levels in the AD group were higher than those in the MCI and HC groups. Moreover, concentrations of sTREM2 in CSF were substantially higher in the MCI group than in the HC group, indicating that CSF sTREM2 levels could be used not only to distinguish between HC and AD patients but also as a biomarker to detect earlier changes in the MCI stage. Conclusions: The results indicate CSF sTREM2 levels reliably predict neurofibrillary degeneration, cognitive decline, and inflammasome activation, and also have a high diagnostic potential for distinguishing diseased from healthy individuals. To add sTREM2 to the list of required AD biomarkers, future studies will need to include a larger number of patients and utilize a standardized methodology.https://www.mdpi.com/2035-8377/15/3/53inflammasomemicrogliamild cognitive impairmentplasma samplestau proteinELISA method |
| spellingShingle | Ena Španić Popovački Mirjana Babić Leko Lea Langer Horvat Klara Brgić Željka Vogrinc Marina Boban Nataša Klepac Fran Borovečki Goran Šimić Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s Disease Neurology International inflammasome microglia mild cognitive impairment plasma samples tau protein ELISA method |
| title | Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s Disease |
| title_full | Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s Disease |
| title_fullStr | Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s Disease |
| title_full_unstemmed | Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s Disease |
| title_short | Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer’s Disease |
| title_sort | soluble trem2 concentrations in the cerebrospinal fluid correlate with the severity of neurofibrillary degeneration cognitive impairment and inflammasome activation in alzheimer s disease |
| topic | inflammasome microglia mild cognitive impairment plasma samples tau protein ELISA method |
| url | https://www.mdpi.com/2035-8377/15/3/53 |
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