| 1. |
-
Overview of the JET results
- 2015
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- De Bastiani, Marco Antônio, et al.
(författare)
-
Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies.
- 2023
-
Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 1090-2139 .- 0889-1591. ; 110, s. 175-184
-
Tidskriftsartikel (refereegranskat)abstract
- In Alzheimer's disease clinical research, glial fibrillary acidic protein (GFAP) released/leaked into the cerebrospinal fluid and blood is widely measured and perceived as a biomarker of reactive astrogliosis. However, it was demonstrated that GFAP levels differ in individuals presenting with amyloid-β (Aβ) or tau pathologies. The molecular underpinnings behind this specificity are little explored. Here we investigated biomarker and transcriptomic associations of hippocampal GFAP-positive astrocytes with Aβ and tau pathologies in humans and mouse models.We studied 90 individuals with plasma GFAP, Aβ- and Tau-PET to investigate the association between biomarkers. Then, transcriptomic analysis in hippocampal GFAP-positive astrocytes isolated from mouse models presenting Aβ (PS2APP) or tau (P301S) pathologies was conducted to explore differentially expressed genes (DEGs), Gene Ontology terms, and protein-protein interaction networks associated with each phenotype.In humans, we found that plasma GFAP associates with Aβ but not tau pathology. Unveiling the unique nature of hippocampal GFAP-positive astrocytic responses to Aβ or tau pathologies, mouse transcriptomics showed scarce overlap of DEGs between the Aβ. and tau mouse models. While Aβ GFAP-positive astrocytes were overrepresented with DEGs associated with proteostasis and exocytosis-related processes, tau hippocampal GFAP-positive astrocytes presented greater abnormalities in functions related to DNA/RNA processing and cytoskeleton dynamics.Our results offer insights into Aβ- and tau-driven specific signatures in hippocampal GFAP-positive astrocytes. Characterizing how different underlying pathologies distinctly influence astrocyte responses is critical for the biological interpretation of astrocyte biomarkers and suggests the need to develop context-specific astrocyte targets to study AD.This study was supported by Instituto Serrapilheira, Alzheimer's Association, CAPES, CNPq and FAPERGS.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Ferrari-Souza, Joao Pedro, et al.
(författare)
-
Vascular risk burden is a key player in the early progression of Alzheimer's disease
- 2024
-
Ingår i: NEUROBIOLOGY OF AGING. - 0197-4580 .- 1558-1497. ; 136, s. 88-98
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding whether vascular risk factors (VRFs) synergistically potentiate Alzheimer's disease (AD) progression is important in the context of emerging treatments for preclinical AD. In a group of 503 cognitively unimpaired individuals, we tested whether VRF burden interacts with AD pathophysiology to accelerate neurodegeneration and cognitive decline. Baseline VRF burden was calculated considering medical data and AD pathophysiology was assessed based on cerebrospinal fluid (CSF) amyloid-beta 1-42 (A beta 1-42) and tau phosphorylated at threonine 181 (p-tau181). Neurodegeneration was assessed with plasma neurofilament light (NfL) and global cognition with the modified version of the Preclinical Alzheimer's Cognitive Composite. The mean (SD) age of participants was 72.9 (6.1) years, and 220 (43.7%) were men. Linear mixed-effects models revealed that an elevated VRF burden synergistically interacted with AD pathophysiology to drive longitudinal plasma NfL increase and cognitive decline. Additionally, VRF burden was not associated with CSF A beta 1-42or p-tau181 changes over time. Our results suggest that VRF burden and AD pathophysiology are independent processes; however, they synergistically lead to neurodegeneration and cognitive deterioration. In preclinical stages, the combination of therapies targeting VRFs and AD pathophysiology might potentiate treatment outcomes.
|
|
| 9. |
- Ferreira, Pamela C. L., et al.
(författare)
-
Endocannabinoid System Biomarkers in Alzheimer's Disease
- 2023
-
Ingår i: CANNABIS AND CANNABINOID RESEARCH. - : Mary Ann Liebert Inc. - 2578-5125 .- 2378-8763. ; 8:1, s. 77-91
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alterations in the endocannabinoid system (ES) have been described in Alzheimer's disease (AD) pathophysiology. In the past years, multiple ES biomarkers have been developed, promising to advance our understanding of ES changes in AD.Discussion: ES biomarkers, including positron emission tomography with cannabinoid receptors tracers and biofluid-based endocannabinoids, are associated with AD disease progression and pathological features.Conclusion: Although not specific enough for AD diagnosis, ES biomarkers hold promise for prognosis, drug-target engagement, and a better understanding of the disease. Here, we summarize currently available ES biomarker findings and discuss their potential applications in the AD research field.
|
|
| 10. |
|
|
