Selective filtering defect at the axon initial segment in Alzheimer's disease mouse models.

Axon pathology has been widely reported in Alzheimer's disease (AD) patients and AD mouse models. Herein we report that increased miR-342-5p down-regulates the expression of ankyrin G (AnkG), a protein known to play a critical role in establishing selective filtering machinery at the axon initial segment (AIS). Diminished AnkG expression leads to defective AIS filtering in cultured hippocampal neurons from AD mouse models, as monitored by selective exclusion of large macromolecules from the axons.

miR-342-5p decreases ankyrin G levels in Alzheimer's disease transgenic mouse models.

MicroRNA alterations and axonopathy have been reported in patients with Alzheimer's disease (AD) and in AD mouse models. We now report that miR-342-5p is upregulated in APP/PS1, PS1ΔE9, and PS1-M146V transgenic AD mice, and that this upregulation is mechanistically linked to elevated β-catenin, c-Myc, and interferon regulatory factor-9. The increased miR-342-5p downregulates the expression of ankyrin G (AnkG), a protein that is known to play a critical role at the axon initial segment.