Journal of Experimental Neurology

Commentary Open Access

Glial Cell and Perineuronal Net Interactions in the Dorsal Striatum of Aged Mice

Zachary A Colon, Alejandro Gamboa, Scott Litwiler, Kathleen A Maguire-Zeiss

Elucidating how normal aging increases vulnerability to neurodegeneration remains a major gap in our understanding of disease risk and progression. The dorsal striatum serves as the primary input nucleus of the basal ganglia and is a key region implicated in multiple neurodegenerative diseases (NDDs). In Colon et al. 2025, we examined the impact of normal aging on neuroinflammatory signaling and perineuronal net (PNN) homeostasis within the dorsal striatum.

Commentary Open Access

An Unusual Ion Channel of the TRP Family TRPV6: A Comment on the Connection of TRPV6 and Mucolipidosis Type II

Claudia Fecher-Trost, Amanda Wyatt, Ulrich Wissenbach

Mutations in a single TRPV6 allele trigger chronic pancreatitis while loss of both alleles is responsible for skeletal dysplasia in newborns. The latter clinical presentation is accompanied by elevated serum levels of the parathyroid hormone, a condition known as transient neonatal hyperparathyroidism (TNHP). In humans, TRPV6 is abundantly expressed in the primary fetal-maternal interface in the placenta, as well as in pancreatic acini and within a few exocrine glands including salivary and lacrimal glands.

Original Research Open Access

Pairwise External Validation of Plasma Biomarker–Based Machine Learning Models for Amyloid PET Prediction: Implications for Calibration and Clinical Utility

Apurva Korni, Ebrahim Zandi

Blood-based biomarkers have demonstrated strong performance for identifying cerebral amyloid pathology within individual cohorts. However, their clinical utility depends on portability across populations and assay platforms. The impact of cross-cohort deployment on clinically actionable metrics such as negative predictive value remains insufficiently characterized. We analyzed data from two independent cohorts: the Alzheimer’s Disease Neuroimaging Initiative (n = 885) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease study (n = 822). 

Commentary Open Access

Commentary: Expanding the Understanding of Gut Microbial Dysbiosis in Alzheimer’s Disease

Sonam Kumari, Mohit Kumar

Alzheimer’s disease (AD) represents a persistent and growing global health challenge. It is a progressive, and largely sporadic neurodegenerative condition characterized not only by a reduction in brain volume and weight but also by widespread and progressive atrophy of the cerebrum. The disease involves substantial loss of neurons, particularly in the hippocampus and the medial temporal lobes, as confirmed through pathological studies.

Commentary Open Access

Resolving Glycosphingosine Isomers by Crown Ether–Assisted Ion Mobility for Neurological Lipidomics

Chao Pang, Sanaz Mohammadzadeh Koumleh, David V. Dearden, Kenneth W. Lee

Glycosphingosines are neuroactive lipids whose stereochemical variations are increasingly implicated in neuronal dysfunction and neurodegenerative disease processes. However, their close structural similarity renders stereoisomer-resolved analysis inaccessible to conventional LC–MS approaches, limiting mechanistic interpretation of lipid-associated neuropathology. In previous work, we demonstrated that complexation of glycosphingosine isomers with crown ethers enabled cyclic ion mobility spectrometry to resolve most of the species. Here, we investigate the energetics and structural effects of crown ether binding to interrogate the mechanism of separation enhancement.

Commentary Open Access

Beyond Clinical Trials: Perampanel across the Lifespan in Contemporary Epilepsy Practice

Anita N. Datta

Perampanel (PER) occupies a singular place in anti-seizure pharmacology. As the only anti-seizure medication (ASM) that acts through selective, non-competitive blockade of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, the principal mediators of fast excitatory neurotransmission in the brain, it brings a mechanistic distinctiveness that sets it apart from agents targeting sodium channels, calcium currents, or synaptic vesicle proteins

Case Report Open Access

Demyelinating Polyneuropathy as the Initial Presentation of Poems Syndrome. The Challenge of Early Diagnosis. A Case Report and Literature Review

Danny Sameh Darwich, Fawaz Ghouse, Adel Kanaan, Shalini Cherala

POEMS syndrome is a rare paraneoplastic multisystemic disorder caused by an underlying monoclonal plasma-cell dyscrasia and characterized by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, and Skin changes. Because early manifestations often overlap with other conditions such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multiple myeloma, diagnosis is frequently delayed.

Commentary Open Access

The Cost of Safety: Balancing Biosafety and Histologic Integrity in Prion Research

Alyssa Seerley, Andrea Grindeland Panter

Prion diseases, or transmissible spongiform encephalopathies (TSEs), represent a group of incurable and invariably fatal neurodegenerative disorders driven by the pathological misfolding of the prion protein (PrP) [1–6]. These diseases are characterized by a progressive clinical course and, despite their significant impact on human [7–17] and animal [1,10,18–30] health, currently lack effective therapeutic interventions [31–34] and are limited in early-stage diagnostics [1,7,31–33]. Given the broad host range of prion diseases, together with the absence of effective treatments and limited antemortem diagnostic options, continued prion disease research remains essential. 

Review Article Open Access

Extracellular Vesicles in Angelman Syndrome: Expanding UBE3A Role beyond a Cell Autonomous Mechanism

Eduardo Penna, Michel Baudry, Xiaoning Bi

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of maternal UBE3A, an E3 ubiquitin ligase essential for neuronal development, synaptic plasticity, and cognitive function. AS has traditionally been viewed as a cell-autonomous disorder in which intracellular UBE3A deficiency drives neuronal dysfunction. However, recent evidence suggests that impaired extracellular vesicle (EV)-mediated intercellular communication also contributes to disease pathophysiology.