Resonant Young's Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers.

The detection of low-molecular-weight biomarkers is essential for diagnosing and managing various diseases, including neurodegenerative conditions such as Alzheimer's disease. A biomarker's low molecular weight is a challenge for label-free optical modalities, as the phase change they detect is directly proportional to the mass bound on the sensor's surface. To address this challenge, we used a resonant Young's slit interferometer geometry and implemented several innovations, such as phase noise matching and optimisation of the fringe spacing, to maximise the signal-to-noise ratio.

Long somatic DNA-repeat expansion drives neurodegeneration in Huntington's disease.

In Huntington's disease (HD), striatal projection neurons (SPNs) degenerate during midlife; the core biological question involves how the disease-causing DNA repeat (CAG) in the huntingtin (HTT) gene leads to neurodegeneration after decades of biological latency. We developed a single-cell method for measuring this repeat's length alongside genome-wide RNA expression. We found that the HTT CAG repeat expands somatically from 40-45 to 100-500+ CAGs in SPNs.

Clinical Diagnoses and Characterization of Patients With Amyloid-Negative Amyloid-Beta, p-Tau, and Neurofilament Light Chain (ATN) Profiles.

The novel amyloid-beta, p-Tau, and neurofilament light chain (ATN) classification scheme has become a promising system for clinically detecting and diagnosing Alzheimer's disease (AD). In addition to its utility in Alzheimer's diagnosis and treatment, the ATN framework may also have clinical relevance in identifying non-Alzheimer's pathologies. In this study conducted at Broadlawns Geriatric and Memory Center, 92 amyloid-negative profiles out of 182 patients with an ATN framework were categorized into subjective cognitive impairment (SCI), non-amnestic mild cognitive impairment (non-amnestic MCI), amnestic MCI, Alzheimer's dementia, vascular dementia, mixed dementia, unspecified dementia, or other memory changes based on diagnoses written in the chart.

Genetic variants in COMT and ESR1 genes shape treatment response to raloxifene in schizophrenia-spectrum disorders.

Background/objective: Raloxifene, a selective estrogen receptor modulator (SERM), may improve symptoms and cognition in schizophrenia spectrum disorders (SSD). Studies have shown inconsistent efficacy, especially in men with SSD. We assessed whether single nucleotide polymorphisms (SNPs) on genes involved in the pharmacodynamics (ESR1 and COMT) and pharmacokinetics (UGT1A8) of raloxifene can explain the heterogeneous treatment response to raloxifene augmentation in patients with SSD.