Recent human trials of treatments for Alzheimer’s disease (AD) have been largely unsuccessful, raising the idea that treatment may need to be started earlier in the disease, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whether amyloid-βAβ? plaque load may serve this purpose. We investigated this in the hAPP-J20 AD mouse model by studying disease pathology at 6, 12, 24 and 36 weeks. Using robust stereological methods, we found there is no neuron loss in the hippocampal CA3 region at any age. However loss of neurons from the hippocampal CA1 region begins as early as 12 weeks of age. The extent of neuron loss increases with age, correlating with the number of activated microglia. Gliosis was also present, but plateaued during aging. Increased hyperactivity and spatial memory deficits occurred at 16 and 24 weeks. Meanwhile, the appearance of plaques and oligomeric Aβ were essentially the last pathological changes, with significant changes only observed at 36 weeks of age. This is surprising given that the hAPP-J20 AD mouse model is engineered to over-expresses Aβ. Our data raises the possibility that plaque load may not be the best marker for early AD and suggests that activated microglia could be a valuable marker to track disease progression.

We demonstrate that within the model of massless Dirac fermions, graphene has a strong nonlinear optical response in the terahertz regime. It is found that the nonlinear contribution significantly alters both the single frequency and frequency tripled optical response at experimentally relevant field strengths. The optical activity of single layer graphene is significantly enhanced by nonlinear effects, and the frequency tripled response opens the gateway to photonic and optoelectronic device applications.

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are comprised of different combinations of GluA1–GluA4 (also known asGluR1–GluR4 and GluR-A to GluR-D) subunits. The GluA2 subunit is subject to RNA editing by the ADAR2 enzyme, which converts a codon for glutamine (Gln; Q), present in the GluA2 gene, to a codon for arginine (Arg; R) found in the mRNA. AMPA receptors are calcium (Ca2+)-permeable if they contain the unedited GluA2(Q) subunit or if they lack the GluA2 subunit. While most AMPA receptors in the brain contain the edited GluA2(R) subunit and are therefore Ca2+-impermeable, recent evidence suggests that Ca2+-permeable AMPA receptors are important in synaptic plasticity, learning, and disease. Strong evidence supports the notion that Ca2+-permeable AMPA receptors are usually GluA2-lacking AMPA receptors, with little evidence to date for a significant role of unedited GluA2 in normal brain function. However, recent detailed studies suggest that Ca2+-permeable AMPA receptors containing unedited GluA2 do in fact occur in neurons and can contribute to excitotoxic cell loss, even where it was previously thought that there was no unedited GluA2.This review provides an update on the role of GluA2 RNA editing in the healthy and diseased brain and summarizes recent insights into the mechanisms that control this process. We suggest that further studies of the role of unedited GluA2 in normal brain function and disease are warranted, and that GluA2 editing should be considered as a possible contributing factor when Ca2+-permeable AMPA receptors are observed.

The competition between Kitaev and Heisenberg interactions away from half filling is studied for the hole-doped Kitaev-Heisenberg t-JK -JH model on a honeycomb lattice. While the isotropic Heisenberg coupling supports a time-reversal violating d-wave singlet state, we find that the Kitaev interaction favors a time-reversal invariant p-wave superconducting phase, which obeys the rotational symmetries of the microscopic model, and is robust for JH < JK /2. Within the p-wave superconducting phase, a critical chemical potential |µ| = µc ≈ t separates a topologically trivial phase for |µ| < µc from a topologically non-trivial Z2 time-reversal invariant spin-triplet phase for |µ| > µc.

Quantum oscillations can be used to determine properties of the Fermi surface of metals by varying the magnitude and orientation of an external magnetic field. Topological insulator surface states are an unusual mix of normal and Dirac fermions. Unlike in graphene and simple metals, Berry's geometric phase in topological insulator surface states is not necessarily quantized. We show that reliably extracting this geometric phase from the phase offset associated with the quantum oscillations is subtle. This is especially so in the presence of a Dirac gap such as that associated with the Zeeman splitting or interlayer tunneling. We develop a semiclassical theory for general mixed normal-Dirac systems in the presence of a gap, and in doing so clarify the role of topology and broken particle-hole symmetry. We propose a systematic procedure of fitting Landau-level index plots at large filling factors to reliably extract the phase offset associated with Berry's phase.