Biology subjects

Helgager, J.

Publications and source records attributed to Helgager, J..

3 recordsLinked to original sources

bioRxiv2026

Amyloid-beta is present in the spinal cord of APP/PS1 mice and may contribute to neuropathology manifesting as lower urinary tract dysfunction

Urinary incontinence (UI) is a common and debilitating comorbidity in Alzheimers disease (AD), yet its underlying pathophysiology remains poorly defined. While UI in dementia has traditionally been attributed to functional impairment, emerging clinical and urodynamic data suggest that neurologic mechanisms may contribute to lower urinary tract dysfunction in this population. Here, we investigated urinary function and neuropathological changes in aged APP/PS1 mice (AD mice), a widely used model of amyloid pathology. Using functional voiding assays, we identified a pattern of urinary dysfunction characterized by increased urinary frequency, small-volume voiding, shortened void duration, and reduced bladder compliance in the absence of bladder outlet obstruction or gross changes in bladder or prostate morphology. These findings are most consistent with a storage-phase abnormality accompanied by impaired voiding coordination rather than classic detrusor overactivity or underactivity. We examined spinal cord and peripheral components involved in bladder innervation and identified amyloid-beta deposition throughout the thoracolumbar and lumbosacral spinal cord, dorsal root ganglia, ventral roots, cauda equina, and associated meningeal structures in AD mice. Importantly, amyloid deposition was accompanied by reduced expression of vesicular acetylcholine transporter and decreased neuronal activation in bladder-innervating pathways, without evidence of increased apoptosis. Taken together, these data demonstrate that AD mice develop a mixed lower urinary tract dysfunction phenotype associated with amyloid-beta deposition and altered neuronal signaling within the spinal cord and peripheral micturition pathways. These findings support a neurogenic contribution to urinary dysfunction in AD and highlight the spinal cord as a novel site of pathology that may influence urinary symptoms in Alzheimers dementia.

neuroscience↗

bioRxiv2026

Structural and Immunological Alterations at the Human Cribriform Plate in Streptococcus pyogenes Meningitis: A Case Study

Streptococcus pyogenes or group A Streptococcus (GAS) meningitis is a rare but deadly infection with a high mortality. Its mechanisms of invasion are unknown, but it has been proposed to enter either through the cribriform plate olfactory nerve bundles or the blood brain barrier. Knowledge of how GAS impacts the cribriform plate olfactory nerves can help us better understand GAS pathogenesis and invasion, as well as how it impacts the olfactory nerve bundles. Here we present the case of a 39-year-old otherwise healthy man who presented to the local emergency department with altered mental status and expired the following day. Neuropathologic examination revealed bacterial leptomeningitis; blood and cerebrospinal fluid cultures both grew Streptococcus pyogenes. Examination of the cribriform plate was notable for perineural accumulation of GAS around certain olfactory nerve bundles. The accumulation around nerves seems to be random and not correlated to size. Nerves that are impacted by GAS as well as nerves that are not impacted display similar levels of gliosis markers GFAP and podoplanin. Neuropeptide Y, a neuropeptide that implicated in neuro-proliferation and hunger was found to colocalize with CD68 positive immune cells within the nasal epithelium, leading to speculations of its involvement in the inflammatory profile during this case of GAS meningitis. Cribriform plate skull channels had undergone width expansion within the patient, pointing towards local bone marrows involvement during infections. These findings are essential to better understanding the human cribriform plates role in CNS immune response and drainage.

neuroscience↗

bioRxiv2018

A single cell-based atlas of human microglial states reveals associations with neurological disorders and histopathological features of the aging brain

Recent studies of bulk microglia have provided insights into the role of this immune cell type in central nervous system development, homeostasis and dysfunction. Nonetheless, our understanding of the diversity of human microglial cell states remains limited; microglia are highly plastic and have multiple different roles, making the extent of phenotypic heterogeneity a central question, especially in light of the development of therapies targeting this cell type. Here, we investigated the population structure of human microglia by single-cell RNA-sequencing. Using surgical- and autopsy-derived cortical brain samples, we identified 14 human microglial subpopulations and noted substantial intra- and inter-individual heterogeneity. These putative subpopulations display divergent associations with Alzheimers disease, multiple sclerosis, and other diseases. Several states show enrichment for genes found in disease-associated mouse microglial states, suggesting additional diversity among human microglia. Overall, human microglia appear to exist in different functional states with varying levels of involvement in different brain pathologies.

neuroscience↗