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.