| 1. |
- Bonham, LW, et al.
(författare)
-
Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
-
Tidskriftsartikel (refereegranskat)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Gao, YX, et al.
(författare)
-
Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
-
Tidskriftsartikel (refereegranskat)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Inguanzo, A, et al.
(författare)
-
MRI data-driven clustering reveals different subtypes of Dementia with Lewy bodies
- 2023
-
Ingår i: NPJ Parkinson's disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 9:1, s. 5-
-
Tidskriftsartikel (refereegranskat)abstract
- Dementia with Lewy bodies (DLB) is a neurodegenerative disorder with a wide heterogeneity of symptoms, which suggests the existence of different subtypes. We used data-driven analysis of magnetic resonance imaging (MRI) data to investigate DLB subtypes. We included 165 DLB from the Mayo Clinic and 3 centers from the European DLB consortium and performed a hierarchical cluster analysis to identify subtypes based on gray matter (GM) volumes. To characterize the subtypes, we used demographic and clinical data, as well as β-amyloid, tau, and cerebrovascular biomarkers at baseline, and cognitive decline over three years. We identified 3 subtypes: an older subtype with reduced cortical GM volumes, worse cognition, and faster cognitive decline (n = 49, 30%); a subtype with low GM volumes in fronto-occipital regions (n = 76, 46%); and a subtype of younger patients with the highest cortical GM volumes, proportionally lower GM volumes in basal ganglia and the highest frequency of cognitive fluctuations (n = 40, 24%). This study shows the existence of MRI subtypes in DLB, which may have implications for clinical workout, research, and therapeutic decisions.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Walker, Z, et al.
(författare)
-
Lewy body dementias
- 2015
-
Ingår i: Lancet (London, England). - 1474-547X. ; 386:10004, s. 1683-1697
-
Tidskriftsartikel (refereegranskat)
|
|
| 37. |
- Walker, Z, et al.
(författare)
-
Lewy Body Dementias
- 2017
-
Ingår i: Focus (American Psychiatric Publishing). - : American Psychiatric Association Publishing. - 1541-4094 .- 1541-4108. ; 15:1, s. 85-100
-
Tidskriftsartikel (refereegranskat)
|
|
| 38. |
|
|
| 39. |
|
|
