Neuronal maturation is altered during pre-pathological stages in the AppNL-F mouse model of Alzheimer's disease

The science

Original title

Neuronal maturation is altered during pre-pathological stages in the AppNL-F mouse model of Alzheimer's disease.

Authors

Doeswijk T, Axenhus M, Malik SC et al.

Journal

Journal of Alzheimer's disease : JAD

Published

Oct 23, 2026

Study type

Study

PMID

42911079 ↗

DOI

10.1177/13872877261491991 ↗

Abstract

BackgroundAn increased understanding of neuronal development in the early stages of Alzheimer's disease (AD) could shed light on the pathogenesis of the disease. Our previous proteomics studies of the knock-in AppNL-F AD mouse model showed changes in neuritogenesis and neurogenesis early in life.ObjectiveWe aimed to characterize neuronal maturation across different stages of the progression of AD.MethodsTo this end, we immunolabeled doublecortin and phosphorylated doublecortin in primary neurons, and brain sections from AppNL-F mice of varying ages and postmortem AD brain.ResultsIncreased doublecortin and decreased phosphorylated doublecortin levels were observed in several cortical regions of embryonic AppNL-F mice. Moreover, increased number of doublecortin positive cells was observed in the hippocampus of 6- and 12-month-old AppNL-F mice. Doublecortin decreased over time in primary neuronal cultures of AppNL-F and wild-type mice in a similar way. Likewise, doublecortin in postmortem human brains did not differ between AD patients and controls.ConclusionsWe conclude that a marker of immature neurons is unchanged in AD patients and aged mice but is altered in the early lifespan of AppNL-F mice, before the onset of symptoms and pathology. These results suggest that neuronal maturation may also be dysregulated in the early, but not later, stages of AD.

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