This paper presents a comprehensive critical overview of fundamental and practical aspects of the modern stripline broadband ferromagnetic resonance (BFMR) spectroscopy largely employed for the ...characterisation of magnetic low-dimensional systems, such as thin ferro- and ferromagnetic, multiferroic and half-metallic films, multi-layers and nanostructures. These planar materials form the platform of the nascent fields of magnonics and spintronics. Experimental and theoretical results of research on these materials are summarised, along with systematic description of various phenomena associated with the peculiarities of the stripline BFMR, such as the geometry of stripline transducers, the orientation of the static magnetic field, the presence of microwave eddy currents, and the impacts of non-magnetic layers, interfaces and surfaces in the samples. Results from 240 articles, textbooks and technical reports are presented and many practical examples are discussed in detail. This review will be of interest to both general physical audience and specialists conducting research on various aspects of magnetisation dynamics and nanomagnetism.
•Low-dimensional magnetic systems form the basis of modern spintronics and magnonics.•We overview the stripline ferromagnetic resonance (FMR) spectroscopy of these materials.•Experimental FMR results on magnetic multilayers and nanostructures are summarised.•The impact of microwave eddy currents on the FMR response of these materials is revealed.•The discussion is supported by results of analytical and numerical modelling.
Spin-wave excitations (magnons) are investigated in a one-dimensional (1D) magnonic crystal fabricated out of Ni80Fe20 nanowires. We find two different magnon band structures depending on the ...magnetic ordering of neighboring wires, i.e., parallel and antiparallel alignment. At a zero in-plane magnetic field H the modes of the antiparallel case are close to those obtained by zone folding of the spin-wave dispersions of the parallel case. This is no longer true for nonzero H which opens a forbidden frequency gap at the Brillouin zone boundary. The 1D stop band gap scales with the external field, which generates a periodic potential for Bragg reflection of the magnons.
Objective
Currently no effective disease‐modifying agents exist for the treatment of Alzheimer disease (AD). The Fyn tyrosine kinase is implicated in AD pathology triggered by amyloid‐ß oligomers ...(Aßo) and propagated by Tau. Thus, Fyn inhibition may prevent or delay disease progression. Here, we sought to repurpose the Src family kinase inhibitor oncology compound, AZD0530, for AD.
Methods
The pharmacokinetics and distribution of AZD0530 were evaluated in mice. Inhibition of Aßo signaling to Fyn, Pyk2, and Glu receptors by AZD0530 was tested by brain slice assays. After AZD0530 or vehicle treatment of wild‐type and AD transgenic mice, memory was assessed by Morris water maze and novel object recognition. For these cohorts, amyloid precursor protein (APP) metabolism, synaptic markers (SV2 and PSD‐95), and targets of Fyn (Pyk2 and Tau) were studied by immunohistochemistry and by immunoblotting.
Results
AZD0530 potently inhibits Fyn and prevents both Aßo‐induced Fyn signaling and downstream phosphorylation of the AD risk gene product Pyk2, and of NR2B Glu receptors in brain slices. After 4 weeks of treatment, AZD0530 dosing of APP/PS1 transgenic mice fully rescues spatial memory deficits and synaptic depletion, without altering APP or Aß metabolism. AZD0530 treatment also reduces microglial activation in APP/PS1 mice, and rescues Tau phosphorylation and deposition abnormalities in APP/PS1/Tau transgenic mice. There is no evidence of AZD0530 chronic toxicity.
Interpretation
Targeting Fyn can reverse memory deficits found in AD mouse models, and rescue synapse density loss characteristic of the disease. Thus, AZD0530 is a promising candidate to test as a potential therapy for AD. Ann Neurol 2015;77:953–971
Amyloid-beta (Aβ) oligomers are thought to trigger Alzheimer's disease pathophysiology. Cellular prion protein (PrP(C)) selectively binds oligomeric Aβ and can mediate Alzheimer's disease-related ...phenotypes. We examined the specificity, distribution and signaling of Aβ-PrP(C) complexes, seeking to understand how they might alter the function of NMDA receptors (NMDARs) in neurons. PrP(C) is enriched in postsynaptic densities, and Aβ-PrP(C) interaction leads to Fyn kinase activation. Soluble Aβ assemblies derived from the brains of individuals with Alzheimer's disease interacted with PrP(C) to activate Fyn. Aβ engagement of PrP(C)-Fyn signaling yielded phosphorylation of the NR2B subunit of NMDARs, which was coupled to an initial increase and then a loss of surface NMDARs. Aβ-induced dendritic spine loss and lactate dehydrogenase release required both PrP(C) and Fyn, and human familial Alzheimer's disease transgene-induced convulsive seizures did not occur in mice lacking PrP(C). These results delineate an Aβ oligomer signal transduction pathway that requires PrP(C) and Fyn to alter synaptic function, with deleterious consequences in Alzheimer's disease.
Progranulin (PGRN) is implicated in Alzheimer’s disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common
GRN
rs5848 variant that results in ...reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the
GRN
AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the
GRN
AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer’s disease neuroimaging initiative studies. Consistent with the human data, subsequent analyses using the APPswe/PS1ΔE9 (APP/PS1) mouse model of cerebral amyloidosis show that PGRN deficiency has no exacerbating effects on Aβ pathology. In contrast and unexpectedly, PGRN deficiency significantly reduces diffuse Aβ plaque growth in these APP/PS1 mice. This protective effect is due, at least in part, to enhanced microglial Aβ phagocytosis caused by PGRN deficiency-induced expression of TYROBP network genes (TNG) including an AD risk factor
Trem2.
PGRN-deficient APP/PS1 mice also exhibit less severe axonal dystrophy and partially improved behavior phenotypes. While PGRN deficiency reduces these amyloidosis-related phenotypes, other neuronal injury mechanisms are increased by loss of PGRN, revealing a multidimensional interaction of
GRN
with AD. For example, C1q complement deposition at synapses is enhanced in APP/PS1 mice lacking PGRN. Moreover, PGRN deficiency increases tau AT8 and AT180 pathologies in human P301L tau-expressing mice. These human and rodent data suggest that global PGRN reduction induces microglial TNG expression and increases AD risk by exacerbating neuronal injury and tau pathology, rather than by accelerating Aβ pathology.
Alzheimer's disease-related phenotypes in mice can be rescued by blockade of either cellular prion protein or metabotropic glutamate receptor 5. We sought genetic and biochemical evidence that these ...proteins function cooperatively as an obligate complex in the brain. We show that cellular prion protein associates via transmembrane metabotropic glutamate receptor 5 with the intracellular protein mediators Homer1b/c, calcium/calmodulin-dependent protein kinase II, and the Alzheimer's disease risk gene product protein tyrosine kinase 2 beta. Coupling of cellular prion protein to these intracellular proteins is modified by soluble amyloid-β oligomers, by mouse brain Alzheimer's disease transgenes or by human Alzheimer's disease pathology. Amyloid-β oligomer-triggered phosphorylation of intracellular protein mediators and impairment of synaptic plasticity in vitro requires Prnp-Grm5 genetic interaction, being absent in transheterozygous loss-of-function, but present in either single heterozygote. Importantly, genetic coupling between Prnp and Grm5 is also responsible for signalling, for survival and for synapse loss in Alzheimer's disease transgenic model mice. Thus, the interaction between metabotropic glutamate receptor 5 and cellular prion protein has a central role in Alzheimer's disease pathogenesis, and the complex is a potential target for disease-modifying intervention.
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