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This research aims to identify early physiological changes in cortical neurons preceding amyloid pathology in a mild Alzheimer's model.

April 11, 2026Scientific ReportsOpen Access

Prodromal changes in cortical neuron physiology before amyloid pathology in a mild model of Alzheimer’s disease

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Observational study investigates neuron changes in a mild Alzheimer’s model, suggesting early biomarkers.

This research aims to identify early physiological changes in cortical neurons preceding amyloid pathology in a mild Alzheimer's model.
Used whole-cell patch-clamp recordings to study neocortical neuron properties.
Analyzed neurons at prodromal (P40-P90) and early symptomatic (P200) stages.
Conducted calcium imaging on primary cortical cultures.
Performed NMR-based metabolomic profiling for neurotransmitter analysis.
NLGF+ neurons showed a depolarized resting membrane potential and enhanced hyperpolarization-activated currents after plaque emergence.
Increased action potential firing and reduced EPSC amplitude were observed alongside elevated EPSC frequency.
Heightened susceptibility to 4-aminopyridine-induced epileptiform activity was noted.
Gap junction blockade with carbenoxolone effectively suppressed hyperexcitability.
No consistent differences in neurotransmitter levels were found across genotypes.

Miličević et al. (2026) studied this question.

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