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

• DOI: 10.1073/pnas.1411837111
• Publication Date: 2014-09-18T03:33:28Z
• Authors: Xiaqin Sun; Yu Wu; Mingxue Gu; Zhuo Liu; Yuanlin Ma; Jun Li; Yan Zhang
• Keywords: Ankyrins; Male; 0303 health sciences; Down-Regulation; Mice, Transgenic; Receptors, N-Methyl-D-Aspartate; Axons; Amyloid beta-Protein Precursor; Disease Models, Animal; Mice; MicroRNAs; 03 medical and health sciences; Alzheimer Disease; Presenilin-1; Animals; Humans; Mutant Proteins; Cells, Cultured

SignificanceIt is widely accepted that Alzheimer’s disease (AD) is an age-related disease that is always associated with later stages of life. However, our data indicates that if carrying familial AD mutations (such as the PS1 mutations examined in this study), neurons are perturbed during development, protein trafficking, protein translocation, and axon initial segment (AIS) subcellular structure formation. Given that AIS is associated with action potential generation and NR2B is highly related to synaptic transmission, we think that this may subsequently lead to many problems associated with misfiring and synaptic transmission in these AD neurons, and may further contribute to AD development and pathology.