Recognizing multiple neuropathological entities in people with dementia improves understanding of diagnosis, prognosis, and expected outcomes from therapies. Care for the individual with dementia includes the evaluation and management of diseases associated with the aged brain, most commonly neurodegeneration and vascular brain injury (VBI). Terminology has evolved to keep pace with diagnostic, prognostic, and therapeutic advances, and autopsy studies have shown that multiple comorbid neuropathological entities are the rule, not the exception, especially in older individuals. With the advent of disease-modifying therapies, delivering dementia care requires an encompassing framework that allows clinicians to consider all of an individual's underlying diseases and their contributions to symptom burden. A diagnostic approach, common co-occurring pathologies, and implications for current and future clinical care are reviewed.

Lewy bodies and neurofibrillary tangles, composed of α-synuclein (α-syn) and tau, respectively, often are found together in the same brain and correlate with worsening cognition. Human postmortem studies show colocalization of α-syn and tau occurs in Lewy bodies, but with limited effort to quantify colocalization. In this study, postmortem middle temporal gyrus tissue from decedents (n = 9) without temporal lobe disease (control) or with Lewy body disease (LBD) was immunofluorescently labeled with antibodies to phosphorylated α-syn (p-α-syn), tau phosphorylated at Ser202/Thr205 (p-tau), or exposure of taus phosphatase-activating domain (PAD-tau) as a marker of early tau aggregates. Immunofluorescence for major-histocompatibility complex class 2 (MHCII) and ionized calcium binding adaptor molecule 1 (Iba1) also was performed because inflammation is an additional pathological hallmark of LBDs, and they were a positive control for two markers known to colocalize. The abundance of p-α-syn, p-tau, and MHCII was significantly associated with diagnosis of LBD. Quantification of colocalization showed that MHCII and Iba1 colocalized, demonstrating activated immune cells are mostly microglia. However, p-α-syn rarely colocalized with p-tau or PAD-tau, although the overlap of p-α-syn with PAD-tau was significantly associated with LBD. In the rare cases pathologic α-syn and pathologic tau were found in the same Lewy body or Lewy neurite, tau appeared to surround α-syn but did not colocalize within the same structure. The relationship between tau and α-syn copathology is important for explaining clinical symptoms, severity, and progression, but there is no evidence for frequent, direct protein-protein interactions in the middle temporal gyrus.

Abstract: Background: Lewy body disease (LBD) often co‐occurs with Alzheimer’s (AD), resulting in more significant cognitive decline than AD or LBD alone. LBD’s hallmarks, asyn‐positive Lewy bodies and neurites, propagate from the enteric system or olfactory bulb to the amygdala, which acts as a gatekeeper for spread to other structures. Initially, LBD appears in the central or cortical nuclei, reflecting brainstem or olfactory origins. A third pattern of LBD is quite prevalent in sporadic and familial early‐onset AD (EOAD). This amygdala‐predominant LBD (AP‐LBD) type does not conform with the most used staging systems for LBD and has received little attention. We found a link between asyn seeding‐competent fibrils in cerebrospinal fluid (CSF) and LBD’s transition from the amygdala, supporting its gatekeeper role. The factors enabling asyn propagation in the amygdala remain unknown. Our goal is to map asyn and tau markers in EOAD cases with permissive vs. non‐permissive AP‐LBD in amygdala subnuclei, identifying spread pathways and vulnerable cell populations. Method: We identified all postmortem EOAD cases with AP‐LBD from the UCSF Neurodegenerative Disease Brain Bank (n = 47), 14 of which have banked CSF for asyn seeding amplification testing. We are using multiplex immunofluorescence to label: phosphorylated asyn; phosphorylated, mis‐conformed, or truncated tau; and all neurons. Markers will be quantified from digital pathology scans, and we will analyze the degree of colocalization by region for the central nucleus, basolateral nuclei, and cortical nucleus. Result: Pending analysis, we will report the pattern of LBD across subnuclei. Of eight CSF samples, 37.5% were positive for asyn seeding with six samples pending. Asyn and tau markers by subnucleus will be compared between CSF‐positive and ‐negative cases. Conclusion: Mapping AP‐LBD across amygdala subnuclei may yield insights into selectively vulnerable neurons. This research has the potential to enhance our understanding of AP‐LBD and its underlying mechanisms, ultimately contributing to the development of more targeted diagnostic and therapeutic strategies in the realm of neurodegenerative diseases.

Black carbon (BC) absorbs solar radiation, leading to a strong but uncertain warming effect on climate. A key challenge in modeling and quantifying BC's radiative effect on climate is predicting enhancements in light absorption that result from internal mixing between BC and other aerosol components. Modeling and laboratory studies show that BC, when mixed with other aerosol components, absorbs more strongly than pure, uncoated BC; however, some ambient observations suggest more variable and weaker absorption enhancement. We show that the lower-than-expected enhancements in ambient measurements result from a combination of two factors. First, the often used spherical, concentric core-shell approximation generally overestimates the absorption by BC. Second, and more importantly, inadequate consideration of heterogeneity in particle-to-particle composition engenders substantial overestimation in absorption by the total particle population, with greater heterogeneity associated with larger model-measurement differences. We show that accounting for these two effects-variability in per-particle composition and deviations from the core-shell approximation-reconciles absorption enhancement predictions with laboratory and field observations and resolves the apparent discrepancy. Furthermore, our consistent model framework provides a path forward for improving predictions of BC's radiative effect on climate.

We report global observations of high-m poloidal waves during the recovery phase of the 22 June 2015 magnetic storm from a constellation of widely spaced satellites of five missions including Magnetospheric Multiscale (MMS), Van Allen Probes, Time History of Events and Macroscale Interactions during Substorm (THEMIS), Cluster, and Geostationary Operational Environmental Satellites (GOES). The combined observations demonstrate the global spatial extent of storm time poloidal waves. MMS observations confirm high azimuthal wave numbers (m ~ 100). Mode identification indicates the waves are associated with the second harmonic of field line resonances. The wave frequencies exhibit a decreasing trend as L increases, distinguishing them from the single-frequency global poloidal modes normally observed during quiet times. Detailed examination of the instantaneous frequency reveals discrete spatial structures with step-like frequency changes along L. Each discrete L shell has a steady wave frequency and spans about 1 R_E , suggesting that there exist a discrete number of drift-bounce resonance regions across L shells during storm times.

We present a statistical study of dipolarization fronts (DFs), using magnetic field data from MMS and Cluster, at radial distances below 12 R_E and 20 R_E , respectively. Assuming that the DFs have a semicircular cross section and are propelled by the magnetic tension force, we used multispacecraft observations to determine the DF velocities. About three quarters of the DFs propagate earthward and about one quarter tailward. Generally, MMS is in a more dipolar magnetic field region and observes larger-amplitude DFs than Cluster. The major findings obtained in this study are as follows: (1) At MMS ∼57 % of the DFs move faster than 150 km/s, while at Cluster only ∼35 %, indicating a variable flux transport rate inside the flow-braking region. (2) Larger DF velocities correspond to higher B_z  values directly ahead of the DFs. We interpret this as a snow plow-like phenomenon, resulting from a higher magnetic flux pileup ahead of DFs with higher velocities.

Introduction

Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood.

Methods

Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N = 56). Diagnostic performance and clinicopathological correlations were examined.

Results

Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%).

Discussion

In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts.

Highlights

A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses.

Multi-particle momentum imaging experiments are now capable of providing detailed information on the properties and the dynamics of quantum systems in Atomic, Molecular and Photon (AMO) physics. Historically, Otto Stern can be considered the pioneer of high-resolution momentum measurements of particles moving in a vacuum and he was the first to obtain sub-atomic unit (a.u.) momentum resolution (Schmidt-Böcking et al. in The precision limits in a single-event quantum measurement of electron momentum and position, these proceedings [1]). A major contribution to modern experimental atomic and molecular physics was his so-called molecular beam method [2], which Stern developed and employed in his experiments. With this method he discovered several fundamental properties of atoms, molecules and nuclei [2, 3]. As corresponding particle detection techniques were lacking during his time, he was only able to observe the averaged footprints of large particle ensembles. Today it is routinely possible to measure the momenta of single particles, because of the tremendous progress in single particle detection and data acquisition electronics. A "state-of-the-art" COLTRIMS reaction microscope [4-11] can measure, for example, the momenta of several particles ejected in the same quantum process in coincidence with sub-a.u. momentum resolution. Such setups can be used to visualize the dynamics of quantum reactions and image the entangled motion of electrons inside atoms and molecules. This review will briefly summarize Stern's work and then present in longer detail the historic steps of the development of the COLTRIMS reaction microscope. Furthermore, some benchmark results are shown which initially paved the way for a broad acceptance of the COLTRIMS approach. Finally, a small selection of milestone work is presented which has been performed during the last two decades.

We report on field-aligned current observations by the four Magnetospheric Multiscale (MMS) spacecraft near the plasma sheet boundary layer (PSBL) during two major substorms on 23 June 2015. Small-scale field-aligned currents were found embedded in fluctuating PSBL flux tubes near the separatrix region. We resolve, for the first time, short-lived earthward (downward) intense field-aligned current sheets with thicknesses of a few tens of kilometers, which are well below the ion scale, on flux tubes moving equatorward/earthward during outward plasma sheet expansion. They coincide with upward field-aligned electron beams with energies of a few hundred eV. These electrons are most likely due to acceleration associated with a reconnection jet or high-energy ion beam-produced disturbances. The observations highlight coupling of multiscale processes in PSBL as a consequence of magnetotail reconnection.