Article ; Online: Cerebrospinal Fluid sTREM-2, GFAP, and β-S100 in Symptomatic Sporadic Alzheimer's Disease: Microglial, Astrocytic, and APOE Contributions Along the Alzheimer's Disease Continuum.
Journal of Alzheimer's disease : JAD
2023 Volume 92, Issue 4, Page(s) 1385–1397
Abstract: Background: Many transversal mechanisms act synergistically at different time-points in the cascade of Alzheimer's disease (AD), since amyloid-β (Aβ) deposition, tau pathology, and neuroinflammation influence each other.: Objective: We explored the ... ...
| Abstract | Background: Many transversal mechanisms act synergistically at different time-points in the cascade of Alzheimer's disease (AD), since amyloid-β (Aβ) deposition, tau pathology, and neuroinflammation influence each other. Objective: We explored the contributions of microglia and astrocytes in patients with symptomatic sporadic AD stratified according to AT(N) system and APOE genotype. Methods: We compared the cerebrospinal fluid (CSF) levels of sTREM-2 and markers of astrocytic activation (GFAP; β-S100) from 71 patients with AD (23 A+T-,48 A+T+; 38 APOEɛ3, 33 APOEɛ4) and 30 healthy controls (HC). With multivariate analyses we investigated associations between glial biomarkers, Aβ42, and p-tau in all subgroups. Results: CSF sTREM-2 was higher in A+T+ [1.437 (0.264)] and A+T- [1.355 (0.213)] than in HC [1.042 (0.198); both p < 0.001]; GFAP and β-S100 were comparable across groups. Considering all patients, sTREM-2 positively associated with Aβ42 (p = 0.04) and p-tau (=0.016), with the first being present only in the A+T- subgroup (p = 0.023). GFAP positively associated with Aβ42 in all patients (p = 0.020) and in the A+T+ subgroup (p = 0.04). Stratifying by APOE, a positive association of sTREM-2 and p-tau was confirmed selectively in carriers of ɛ4 (p = 0.018). Finally, sTREM-2 positively correlated with β-S100 in all subgroups, and with GFAP in A+T+ (p = 0.042). Conclusion: Our results confirm the increase of CSF sTREM-2 in AD, which associates with reduced amyloidopathy in A+T- patients. Moreover, microglial activation seems to increase CSF tau levels in carriers of APOEɛ4, is associated with astrocytic reactivity (GFAP) in A+T+, and likely leads the acquisition of a more neurotoxic astrocytic phenotype (β-S100). |
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| MeSH term(s) | Humans ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/cerebrospinal fluid ; Apolipoproteins E/genetics ; Astrocytes/pathology ; Biomarkers/cerebrospinal fluid ; Microglia/pathology ; Peptide Fragments/cerebrospinal fluid ; tau Proteins/cerebrospinal fluid |
| Chemical Substances | Amyloid beta-Peptides ; Apolipoproteins E ; Biomarkers ; Peptide Fragments ; tau Proteins ; S100B protein, human ; TREM2 protein, human ; GFAP protein, human |
| Language | English |
| Publishing date | 2023-02-24 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 1440127-7 |
| ISSN | 1875-8908 ; 1387-2877 |
| ISSN (online) | 1875-8908 |
| ISSN | 1387-2877 |
| DOI | 10.3233/JAD-221010 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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