Diagnosing Alzheimer's Disease from Circulating Blood Leukocytes Using a Fluorescent Amyloid Probe

BACKGROUND: Toxic amyloid-β (Aβ) peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. Given the prominent role of the immune system, phagocytic blood cells may contact pathological brain materials. OBJECTIVE: To develop a novel method for early Alzheimer's disease (AD) detection, we used blood leukocytes, that could act as "sentinels" after trafficking through the brain microvasculature, to detect pathological amyloid by labelling with a conformationally-sensitive fluorescent amyloid probe and imaging with confocal spectral microscopy. METHODS: Formalin-fixed peripheral blood mononuclear cells (PBMCs) from cognitively healthy control (HC) subjects, mild cognitive impairment (MCI) and AD patients were stained with the fluorescent amyloid probe K114, and imaged. Results were validated against cerebrospinal fluid (CSF) biomarkers and clinical diagnosis. RESULTS: K114-labeled leukocytes exhibited distinctive fluorescent spectral signatures in MCI/AD subjects. Comparing subjects with single CSF biomarker-positive AD/MCI to negative controls, our technique yielded modest AUCs, which improved to the 0.90 range when only MCI subjects were included in order to measure performance in an early disease state. Combining CSF Aβ 42 and t-Tau metrics further improved the AUC to 0.93. CONCLUSION: Our method holds promise for sensitive detection of AD-related protein misfolding in circulating leukocytes, particularly in the early stages of disease

The AdS 3 × S 3 × S 3 × S 1 worldsheet S matrix

We investigate type IIB strings on AdS 3 × S 3 × S 3 × S 1 with mixed Ramond–Ramond and Neveu–Schwarz–Neveu–Schwarz flux. By suitably gauge-fixing the closed string Green–Schwarz action of this theory, we derive the off-shell symmetry algebra and its representations. We use these to determine the non-perturbative worldsheet S matrix of fundamental excitations in the theory. The analysis involves both massive and massless modes in complete generality. The S matrix we find involves a number of phase factors, which in turn satisfy crossing equations that we also determine. We comment on the nature of the heaviest modes of the theory, but leave their identification either as composites or bound-states to a future investigation

On the dressing factors, Bethe equations and Yangian symmetry of strings on AdS3 × S3 × T4

Integrability is believed to underlie the AdS3/CFT2 correspondence with sixteen supercharges. We elucidate the role of massless modes within this integrable framework. Firstly, we find the dressing factors that enter the massless and mixed-mass worldsheet S matrix. Secondly, we derive a set of all-loop Bethe Equations for the closed strings, determine their symmetries and weak-coupling limit. Thirdly, we investigate the underlying Yangian symmetry in the massless sector and show that it fits into the general framework of Yangian integrability. In addition, we compare our S matrix in the near-relativistic limit with recent perturbative worldsheet calculations of Sundin and Wulff

The non-integrability of strings in massive type IIA and their holographic duals

In this work we study various aspects of six-dimensional ${\cal N}=(1,0)$ SCFTs. We consider the construction of their string duals in Massive IIA and discuss some observables in given examples. We study the dynamics of string solitons wrapping and rotating on the Massive IIA background and show that the associated Hamiltonian system is both non-integrable and chaotic, implying the non-integrability of the dual CFT. Our procedure is analytic, using well developed mathematical techniques, and numerical, by the explicit calculation of power spectra, Lyapunov coefficients and Poincar\'e sections.Comment: 28 pages plus appendices. Various figures. Some clarifications and references adde