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- Mendonça, Clarissa Ferolla, et al.
(författare)
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Proteomic signatures of brain regions affected by tau pathology in early and late stages of Alzheimer's disease
- 2019
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 130
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder. Depositions of amyloid β peptide (Aβ) and tau protein are among the major pathological hallmarks of AD. Aβ and tau burden follows predictable spatial patterns during the progression of AD. Nevertheless, it remains obscure why certain brain regions are more vulnerable than others; to investigate this and dysregulated pathways during AD progression, a mass spectrometry-based proteomics study was performed. Methods: In total 103 tissue samples from regions early (entorhinal and parahippocampal cortices - medial temporal lobe (MTL)) and late affected (temporal and frontal cortices - neocortex) by tau pathology were subjected to label-free quantitative proteomics analysis. Results: Considering dysregulated proteins during AD progression, the majority (625 out of 737 proteins) was region specific, while some proteins were shared between regions (101 proteins altered in two areas and 11 proteins altered in three areas). Analogously, many dysregulated pathways during disease progression were exclusive to certain regions, but a few pathways altered in two or more areas. Changes in protein expression indicate that synapse loss occurred in all analyzed regions, while translation dysregulation was preponderant in entorhinal, parahippocampal and frontal cortices. Oxidative phosphorylation impairment was prominent in MTL. Differential proteomic analysis of brain areas in health state (controls) showed higher metabolism and increased expression of AD-related proteins in the MTL compared to the neocortex. In addition, several proteins that differentiate brain regions in control tissue were dysregulated in AD. Conclusions: This work provides the comparison of proteomic changes in brain regions affected by tau pathology at different stages of AD. Although we identified commonly regulated proteins and pathways during disease advancement, we found that the dysregulated processes are predominantly region specific. In addition, a distinct proteomic signature was found between MTL and neocortex in healthy subjects that might be related to AD vulnerability. These findings highlight the need for investigating AD's cascade of events throughout the whole brain and studies spanning more brain areas are required to better understand AD etiology and region vulnerability to disease.
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| 2. |
- Paciaroni, Maurizio, et al.
(författare)
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Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke.
- 2019
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Ingår i: European stroke journal. - : SAGE Publications. - 2396-9881 .- 2396-9873. ; 4:1, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear.In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation.In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke.A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04)).After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.
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