Mineral Detection of Neutrinos and Dark Matter 2024. Proceedings

The second "Mineral Detection of Neutrinos and Dark Matter" (MDvDM'24) meeting was held January 8-11, 2024 in Arlington, VA, USA, hosted by Virginia Tech's Center for Neutrino Physics. This document collects contributions from this workshop, providing an overview of activities in the field. MDvDM'24 was the second topical workshop dedicated to the emerging field of mineral detection of neutrinos and dark matter, following a meeting hosted by IFPU in Trieste, Italy in October 2022. Mineral detectors have been proposed for a wide variety of applications, including searching for dark matter, measuring various fluxes of astrophysical neutrinos over gigayear timescales, monitoring nuclear reactors, and nuclear disarmament protocols; both as paleo-detectors using natural minerals that could have recorded the traces of nuclear recoils for timescales as long as a billion years and as detectors recording nuclear recoil events on laboratory timescales using natural or artificial minerals. Contributions to this proceedings discuss the vast physics potential, the progress in experimental studies, and the numerous challenges lying ahead on the path towards mineral detection. These include a better understanding of the formation and annealing of recoil defects in crystals; identifying the best classes of minerals and, for paleo-detectors, understanding their geology; modeling and control of the relevant backgrounds; developing, combining, and scaling up imaging and data analysis techniques; and many others. During the last years, MDvDM has grown rapidly and gained attention. Small-scale experimental efforts focused on establishing various microscopic readout techniques are underway at institutions in North America, Europe and Asia. We are looking ahead to an exciting future full of challenges to overcome, surprises to be encountered, and discoveries lying ahead of us.Comment: Summary and proceedings of the MDvDM'24 conference, Jan 8-11 202

A blood-based signature of cerebrospinal fluid A beta(1-42) status

It is increasingly recognized that Alzheimer's disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebrospinal fluid (CSF) amyloid beta(1-42) (A beta(1-42)) may be an earlier indicator of Alzheimer's disease risk than measures of amyloid obtained from Positron Emission Tomography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap. In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an individual's CSF amyloid status using a machine learning approach. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF A beta(1-42) levels indicative of AD risk (0.84 AUC, 0.78 sensitivity, and 0.73 specificity). Refinement of the modeling indicates that only APOE epsilon 4 carrier status and four plasma analytes (CGA, A beta(1-42), Eotaxin 3, APOE) are required to achieve a high level of accuracy. Furthermore, we show across an independent validation cohort that individuals with predicted abnormal CSF A beta(1-42) levels transitioned to an AD diagnosis over 120 months significantly faster than those with predicted normal CSF A beta(1-42) levels and that the resulting model also validates reasonably across PET A beta(1-42) status (0.78 AUC). This is the first study to show that a machine learning approach, using plasma protein levels, age and APOE epsilon 4 carrier status, is able to predict CSF A beta(1-42) status, the earliest risk indicator for AD, with high accuracy