The future of AD clinical trials with the advent of anti-amyloid therapies: An CTAD Task Force report

BACKGROUND: Aducanumab (ADUHELMTM) was approved for the treatment of Alzheimer\u27s disease (AD) in the US. This approval was supported by an effect on the cerebral amyloid plaque load and evidence of cognitive efficacy to be confirmed in post-marketing trials. Other anti-amyloid antibodies are under investigation in phase III (donanemab, lecanemab, gantenerumab) and have shown preliminary evidence of a cognitive benefit in phase II trials. Although these agents target a small segment of patients with mild cognitive impairment due to AD or mild AD dementia, their advent will change the design of future clinical trials both for anti-amyloid and non-amyloid drugs. These changes will promote the selection of patients in clinical trials by amyloid and tau biomarkers that identify patients with appropriate biology and may follow the treatment response to approved amyloid antibodies. The use of these agents creates the opportunity to test combined drug therapies and to conduct comparative assessments with innovative therapies and newly approved drugs available in clinical practice. Blood-based AD biomarkers should be implemented in research and could facilitate the recruitment into clinical trials. Anti-amyloid antibodies will have positive (e.g., more early diagnosis) and negative impacts (some subjects will be reluctant to participate in trials and risk assignment to placebo) on AD trials in the immediate future. We present the results of the CTAD Task Force on this topic, in Boston, November 6, 2021

Thermodynamics and magnetic field profiles in low-kappa type-II superconductors

Two-dimensional low-kappa type-II superconductors are studied numerically within the Eilenberger equations of superconductivity. Depending on the Ginzburg-Landau parameter \kappa=\lambda/\xi vortex-vortex interaction can be attractive or purely repulsive. The sign of interaction is manifested as a first (second) order phase transition from Meissner to the mixed state. Temperature and field dependence of the magnetic field distribution in low-kappa type-II superconductors with attractive intervortex interaction is calculated. Theoretical results are compared to the experiment.Comment: 4 pages, 3 figure

Domain walls at the spin density wave endpoint of the organic superconductor (TMTSF)2PF6 under pressure

We report the first comprehensive investigation of the organic superconductor (TMTSF)2PF6 in the vicinity of the endpoint of the spin density wave - metal phase transition where phase coexistence occurs. At low temperature, the transition of metallic domains towards superconductivity is used to reveal the various textures. In particular, we demonstrate experimentally the existence of 1D and 2D metallic domains with a cross-over from a filamentary superconductivity mostly along the c?-axis to a 2D superconductivity in the b?c-plane perpendicular to the most conducting direction. The formation of these domain walls may be related to the proposal of a soliton phase in the vicinity of the critical pressure of the (TMTSF)2PF6 phase diagram.Comment: 5 page

Spin-density wave versus superconducting fluctuations for quasi-one-dimensional electrons in two chains of Tomonaga-Luttinger liquids

We study possible states at low temperatures by applying the renormalization-group method to two chains of Tomonaga-Luttinger liquids with both repulsive intrachain interactions and interchain hopping. As the energy decreases below the hopping energy, three distinct regions I, III, and II appear successively depending on properties of fluctuations. The crossover from the spin-density wave (SDW) state to superconducting (SC) state takes place in region III where there are the excitation gaps of transverse charge and spin fluctuations. The competition between SDW and SC states in region III is crucial to understanding the phase diagram in the quasi-one-dimensional organic conductors.Comment: 11 pages, Revtex format, 1 figure, to be published in Phys. Rev.

Spin-triplet superconductivity in quasi-one dimension

We consider a system with electron-phonon interaction, antiferromagnetic fluctuations and disconnected open Fermi surfaces. The existence of odd-parity superconductivity in this circumstance is shown for the first time. If it is applied to the quasi-one-dimensional systems like the organic conductors (TMTSF)_2X we obtain spin-triplet superconductivity with nodeless gap. Our result is also valid in higher dimensions(2d and 3d).Comment: 2 page

Role of Phase Variables in Quarter-Filled Spin Density Wave States

Several kinds of spin density wave (SDW) states with both quarter-filled band and dimerization are reexamined for a one-dimensional system with on-site, nearest-neighbor and next-nearest-neighbor repulsive interactions, which has been investigated by Kobayashi et al. (J. Phys. Soc. Jpn. 67 (1998) 1098). Within the mean-field theory, the ground state and the response to the density variation are calculated in terms of phase variables, $\theta$ and $\phi$, where $\theta$ expresses the charge fluctuation of SDW and $\phi$ describes the relative motion between density wave with up spin and that with down spin respectively. It is shown that the exotic state of coexistence of 2k_F-SDW and 2k_F-charge density wave (CDW) is followed by 4k_F-SDW but not by 4k_F-CDW where k_F denotes a Fermi wave vector. The harmonic potential with respect to the variation of $\theta$ and/or $\phi$ disappears for the interactions, which lead to the boundary between the pure 2k_F-SDW state and the corresponding coexistent state.Comment: 9 pages, 15 figures, to be published in J. Phys. Soc. Jpn. 69 No.3 (2000) 79

Antiferromagnetic Phases of One-Dimensional Quarter-Filled Organic Conductors

The magnetic structure of antiferromagnetically ordered phases of quasi-one-dimensional organic conductors is studied theoretically at absolute zero based on the mean field approximation to the quarter-filled band with on-site and nearest-neighbor Coulomb interaction. The differences in magnetic properties between the antiferromagnetic phase of (TMTTF)$_2$X and the spin density wave phase in (TMTSF)$_2$X are seen to be due to a varying degrees of roles played by the on-site Coulomb interaction. The nearest-neighbor Coulomb interaction introduces charge disproportionation, which has the same spatial periodicity as the Wigner crystal, accompanied by a modified antiferromagnetic phase. This is in accordance with the results of experiments on (TMTTF)$_2$Br and (TMTTF)$_2$SCN. Moreover, the antiferromagnetic phase of (DI-DCNQI)$_2$Ag is predicted to have a similar antiferromagnetic spin structure.Comment: 8 pages, LaTeX, 4 figures, uses jpsj.sty, to be published in J. Phys. Soc. Jpn. 66 No. 5 (1997

Coexistent State of Charge Density Wave and Spin Density Wave in One-Dimensional Quarter Filled Band Systems under Magnetic Fields

We theoretically study how the coexistent state of the charge density wave and the spin density wave in the one-dimensional quarter filled band is enhanced by magnetic fields. We found that when the correlation between electrons is strong the spin density wave state is suppressed under high magnetic fields, whereas the charge density wave state still remains. This will be observed in experiments such as the X-ray measurement.Comment: 7 pages, 15 figure

Magnetization plateau in a two-dimensional multiple-spin exchange model

We study a multiple-spin exchange model on a triangular lattice, which is a possible model for low-density solid 3He films. Due to strong competitions between ferromagnetic three-spin exchange and antiferromagnetic four-spin one, the ground states are highly degenerate in the classical limit. At least 2^{L/2}-fold degeneracy exists on the L*L triangular lattice except for the SO(3) symmetry. In the magnetization process, we found a plateau at m/m_{sat}=1/2, in which the ground state is "uuud state" (a collinear state with four sublattices). The 1/2-plateau appears due to the strong four-spin exchange interaction. This plateau survives against both quantum and thermal fluctuations. Under a magnetic field which realizes the "uuud" ordered state, a phase transition occurs at a finite temperature. We predict that low-density solid 3He thin films may show the 1/2-plateau in the magnetization process. Experimental observation of the plateau will verify strength of the four-spin exchange. It is also discussed that this magnetization plateau can be understood as an insulating-conducting transition in a particle picture.Comment: 10 pages, RevTeX, 12 figures, added a reference and corrected typos, to be published in Phys.Rev.B (01 APR 99

Possible Triplet Electron Pairing and an Anisotropic Spin Susceptibility in Organic Superconductors (TMTSF)_2 X

We argue that (TMTSF)_2 PF_6 compound under pressure is likely a triplet superconductor with a vector order parameter d(k) \equiv (d_a(k) \neq 0, d_c(k) = ?, d_{b'}(k) = 0); |d_a(k)| > |d_c(k)|. It corresponds to an anisotropic spin susceptibility at T=0: \chi_{b'} = \chi_0, \chi_a \ll \chi_0, where \chi_0 is its value in a metallic phase. [The spin quantization axis, z, is parallel to a so-called b'-axis]. We show that the suggested order parameter explains why the upper critical field along the b'-axis exceeds all paramagnetic limiting fields, including that for a nonuniform superconducting state, whereas the upper critical field along the a-axis (a \perp b') is limited by the Pauli paramagnetic effects [I. J. Lee, M. J. Naughton, G. M. Danner and P. M. Chaikin, Phys. Rev. Lett. 78, 3555 (1997)]. The triplet order parameter is in agreement with the recent Knight shift measurements by I. J. Lee et al. as well as with the early results on a destruction of superconductivity by nonmagnetic impurities and on the absence of the Hebel-Slichter peak in the NMR relaxation rate.Comment: 4 pages, 1 eps figur