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- Vogels, Thomas, et al.
(författare)
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Propagation of Tau Pathology : Integrating Insights From Postmortem and In Vivo Studies
- 2020
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 87:9, s. 808-818
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Forskningsöversikt (refereegranskat)abstract
- Cellular accumulation of aggregated forms of the protein tau is a defining feature of so-called tauopathies such as Alzheimer's disease, progressive supranuclear palsy, and chronic traumatic encephalopathy. A growing body of literature suggests that conformational characteristics of tau filaments, along with regional vulnerability to tau pathology, account for the distinct histopathological morphologies, biochemical composition, and affected cell types seen across these disorders. In this review, we describe and discuss recent evidence from human postmortem and clinical biomarker studies addressing the differential vulnerability of brain areas to tau pathology, its cell-to-cell transmission, and characteristics of the different strains that tau aggregates can adopt. Cellular biosensor assays are increasingly used in human tissue to detect the earliest forms of tau pathology, before overt histopathological lesions (i.e., neurofibrillary tangles) are apparent. Animal models with localized tau expression are used to uncover the mechanisms that influence spreading of tau aggregates. Further, studies of human postmortem-derived tau filaments from different tauopathies injected in rodents have led to striking findings that recapitulate neuropathology-based staging of tau. Furthermore, the recent advent of tau positron emission tomography and novel fluid-based biomarkers render it possible to study the temporal progression of tau pathology in vivo. Ultimately, evidence from these approaches must be integrated to better understand the onset and progression of tau pathology across tauopathies. This will lead to improved methods for the detection and monitoring of disease progression and, hopefully, to the development and refinement of tau-based therapeutics.
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| 3. |
- Sutovsky, Stanislav, et al.
(författare)
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Atypical Huntington's disease with the clinical presentation of behavioural variant of frontotemporal dementia
- 2016
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 123:12, s. 1423-1433
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease is an incurable, adult-onset, autosomal dominant inherited disorder caused by an expanded trinucleotide repeat (CAG). In this study, we describe a Huntington's disease patient displaying clinical symptoms of the behavioural variant of frontotemporal dementia in the absence of tremor and ataxia. The clinical onset was at the age of 36 years and the disease progressed slowly (18 years). Genetic testing revealed expanded trinucleotide CAG repeats in the Huntingtin gene, together with a Glu318Gly polymorphism in presenilin 1. Neuropathological assessment revealed extensive amyloid beta (A beta) aggregates in all cortical regions. No inclusions displaying hyperphosphorylated tau or phosphorylated transactive response DNA-binding protein 43 (TDP43) were found. A high number of p62 (sequestosome 1) immunopositive intranuclear inclusions were seen mainly in the cortex, while subcortical areas were affected to a lesser extent. Confocal microscopy revealed that the majority of p62 intranuclear lesions co-localised with the fused-in-sarcoma protein (FUS) immunostaining. The morphology of the inclusions resembled intranuclear aggregates in Huntington's disease. The presented proband suffered from Huntington's disease showed atypical distribution of FUS positive intranuclear aggregates in the cortical areas with concomitant Alzheimer's disease pathology.
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