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- Blennow, Kaj, et al.
(author)
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Cerebrospinal fluid tau fragment correlates with tau PET : a candidate biomarker for tangle pathology
- 2020
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 143:2, s. 650-660
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Journal article (peer-reviewed)abstract
- To date, there is no validated fluid biomarker for tau pathology in Alzheimer's disease, with contradictory results from studies evaluating the correlation between phosphorylated tau in CSF with tau PET imaging. Tau protein is subjected to proteolytic processing into fragments before being secreted to the CSF. A recent study suggested that tau cleavage after amino acid 368 by asparagine endopeptidase (AEP) is upregulated in Alzheimer's disease. We used immunoprecipitation followed by mass spectrometric analyses to evaluate the presence of tau368 species in CSF. A novel Simoa® assay for quantification of tau368 in CSF was developed, while total tau (t-tau) was measured by ELISA and the presence of tau368 in tangles was evaluated using immunohistochemistry. The diagnostic utility of tau368 was first evaluated in a pilot study (Alzheimer's disease = 20, control = 20), then in a second cohort where the IWG-2 biomarker criteria were applied (Alzheimer's disease = 37, control = 45), and finally in a third cohort where the correlation with 18F-GTP1 tau PET was evaluated (Alzheimer's disease = 38, control = 11). The tau368/t-tau ratio was significantly decreased in Alzheimer's disease (P < 0.001) in all cohorts. Immunohistochemical staining demonstrated that tau fragments ending at 368 are present in tangles. There was a strong negative correlation between the CSF tau368/t-tau ratio and 18F-GTP1 retention. Our data suggest that tau368 is a tangle-enriched fragment and that the CSF ratio tau368/t-tau reflects tangle pathology. This novel tau biomarker could be used to improve diagnosis of Alzheimer's disease and to facilitate the development of drug candidates targeting tau pathology. Furthermore, future longitudinal studies will increase our understanding of tau pathophysiology in Alzheimer's disease and other tauopathies.
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- Izquierdo, Paula, et al.
(author)
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Fast spectrophotometry of WD 1145+017
- 2018
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 481:1, s. 703-714
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Journal article (peer-reviewed)abstract
- WD 1145+017 is currently the only white dwarf known to exhibit periodic transits of planetary debris as well as absorption lines from circumstellar gas. We present the first simultaneous fast optical spectrophotometry and broad-band photometry of the system, obtained with the Gran Telescopio Canarias (GTC) and the Liverpool Telescope, respectively. The observations spanned 5.5 h, somewhat longer than the 4.5-h orbital period of the debris. Dividing the GTC spectrophotometry into five wavelength bands reveals no significant colour differences, confirming grey transits in the optical. We argue that absorption by an optically thick structure is a plausible alternative explanation for the achromatic nature of the transits that can allow the presence of small-sized (~µm) particles. The longest (87 min) and deepest (50 per cent attenuation) transit recorded in our data exhibits a complex structure around minimum light that can be well modelled by multiple overlapping dust clouds. The strongest circumstellar absorption line, Fe II λ5169, significantly weakens during this transit, with its equivalent width reducing from a mean out-of-transit value of 2 to 1 Å in-transit, supporting spatial correlation between the circumstellar gas and dust. Finally, we made use of the Gaia Data Release 2 and archival photometry to determine the white dwarf parameters. Adopting a helium-dominated atmosphere containing traces of hydrogen and metals, and a reddening E(B - V) = 0.01 we find T_eff=15 020 ± 520 K, log g = 8.07 ± 0.07, corresponding to M_WD=0.63± 0.05 M☉ and a cooling age of 224 ± 30 Myr.
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