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.

Modeling Insights into Potential Mechanisms of Opioid-Induced Respiratory Depression within Medullary and Pontine Networks.

The opioid epidemic is a pervasive health issue and continues to have a drastic impact on the United States. This is primarily because opioids cause respiratory suppression and the leading cause of death in opioid overdose is respiratory failure (, opioid-induced respiratory depression, OIRD). Opioid administration can affect the frequency and magnitude of inspiratory motor drive by activating μ-opioid receptors that are located throughout the respiratory control network in the brainstem.