1,187 research outputs found
Spontaneous ARIA (Amyloid-Related Imaging Abnormalities) and Cerebral Amyloid Angiopathy Related Inflammation in Presenilin 1-Associated Familial Alzheimer's Disease
Amyloid-related imaging abnormalities (ARIA), thought to reflect immune responses to vascular amyloid, have been detected in several amyloid-modifying therapy trials for Alzheimer's disease (AD). We report a case of ARIA developing spontaneously during the course of Presenilin 1 (PSEN1)-associated familial AD (FAD), in an APOE4 homozygous patient. Severe cerebral amyloid angiopathy with associated inflammation was subsequently found at autopsy. Recognition that ARIA may arise spontaneously during FAD and of the potential risk factors for its development are important observations given the recent launch of amyloid-modifying therapy trials for FAD
Catastrophic Fermi surface reconstruction in the shape-memory alloy AuZn
AuZn undergoes a shape-memory transition at 67 K. The de Haas van Alphen
effect persists to 100 K enabling the observation of a change in the quantum
oscillation spectrum indicative of a catastrophic Fermi surface reconstruction
at the transition. Coexistence of both Fermi surfaces at low temperatures is
suggestive of an intrinsic phase separation in the bulk of the material. In
addition, a Dingle analysis reveals a sharp change in the scattering mechanism
at a threshold cyclotron radius, which we suggest to be related to the
underlying microstructure that drives the shape-memory effect.Comment: 4 pages, 4 figure
The novel MAPT mutation K298E:mechanisms of mutant tau toxicity, brain pathology and tau expression in induced fibroblast-derived neurons
Frontotemporal lobar degeneration (FTLD) consists of a group of neurodegenerative diseases characterized by behavioural and executive impairment, language disorders and motor dysfunction. About 20-30 % of cases are inherited in a dominant manner. Mutations in the microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T). Here we report a novel MAPT mutation (K298E) in exon 10 in a patient with FTDP-17T. Neuropathological studies of post-mortem brain showed widespread neuronal loss and gliosis and abundant deposition of hyperphosphorylated tau in neurons and glia. Molecular studies demonstrated that the K298E mutation affects both protein function and alternative mRNA splicing. Fibroblasts from a skin biopsy of the proband taken at post-mortem were directly induced into neurons (iNs) and expressed both 3-repeat and 4-repeat tau isoforms. As well as contributing new knowledge on MAPT mutations in FTDP-17T, this is the first example of the successful generation of iNs from skin cells retrieved post-mortem
Understanding the complex phase diagram of uranium: the role of electron-phonon coupling
We report an experimental determination of the dispersion of the soft phonon
mode along [1,0,0] in uranium as a function of pressure. The energies of these
phonons increase rapidly, with conventional behavior found by 20 GPa, as
predicted by recent theory. New calculations demonstrate the strong pressure
(and momentum) dependence of the electron-phonon coupling, whereas the
Fermi-surface nesting is surprisingly independent of pressure. This allows a
full understanding of the complex phase diagram of uranium, and the interplay
between the charge-density wave and superconductivity
Discriminatory ability of next-generation tau PET tracers for Alzheimer's disease
A next generation of tau PET tracers for imaging of Alzheimer’s disease and other dementias has recently been developed. Whilst the new compounds have now entered clinical studies, there is limited information available to assess their suitability for clinical applications. Head-to-head comparisons are urgently needed to understand differences in the radiotracer binding profiles.
We characterised the binding of the tau tracers PI2620, RO948, MK6240 and JNJ067 in human post-mortem brain tissue from a cohort of 25 dementia cases and age-matched controls, using quantitative phosphorimaging with tritium labelled radiotracers in conjunction with phospho-tau specific immunohistochemistry.
The four tau radiotracers depicted tau inclusions composed of paired helical filaments with high specificity, both in cases with Alzheimer’s disease and in primary tauopathy cases with concomitant Alzheimer’s disease pathology. In contrast, cortical binding to primary tauopathy cases without paired helical filament tau was found to be within the range of age-matched controls. Off-target binding to monoamine oxidase B has been overcome, as demonstrated by heterologous blocking studies in basal ganglia tissue. The high variability of cortical tracer binding within the Alzheimer’s disease group followed the same pattern with each tracer, suggesting that all compounds are suited to differentiate Alzheimer’s disease from other dementias
Fermi Surface of Alpha-Uranium at Ambient Pressure
We have performed de Haas-van Alphen measurements of the Fermi surface of
alpha-uranium single crystals at ambient pressure within the alpha-3 charge
density wave (CDW) state from 0.020 K - 10 K and magnetic fields to 35 T using
torque magnetometry. The angular dependence of the resulting frequencies is
described. Effective masses were measured and the Dingle temperature was
determined to be 0.74 K +/- 0.04 K. The observation of quantum oscillations
within the alpha-3 CDW state gives new insight into the effect of the charge
density waves on the Fermi surface. In addition we observed no signature of
superconductivity in either transport or magnetization down to 0.020 K
indicating the possibility of a pressure-induced quantum critical point that
separates the superconducting dome from the normal CDW phase.Comment: 11 pages, 4 figures, 3 table
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