RT Journal Article
T1 Pyramidal cell axon initial segment in Alzheimer´s disease
A1 Antón Fernández, Alejandro
A1 León Espinosa, Gonzalo
A1 DeFelipe, Javier
A1 Muñoz Céspedes, Alberto
AB The axon initial segment (AIS) is a region of the neuron that is critical for action potential generation as well as for the regulation of neural activity. This specialized structure—characterized by the expression of different types of ion channels as well as adhesion, scaffolding and cytoskeleton proteins—is subjected to morpho-functional plastic changes in length and position upon variations in neural activity or in pathological conditions. In the present study, using immunocytochemistry with the AT8 antibody (phospho-tau S202/T205) and 3D confocal microscopy reconstruction techniques in brain tissue from Alzheimer’s disease patients, we found that around half of the cortical pyramidal neurons with hyperphosphorylated tau showed changes in AIS length and position in comparison with AT8-negative neurons from the same cortical layers. We observed a wide variety of AIS alterations in neurons with hyperphosphorylated tau, although the most common changes were a proximal shift or a lengthening of the AISs. Similar results were found in neocortical tissue from non-demented cases with neurons containing hyperphosphorylated tau. These findings support the notion that the accumulation of phospho-tau is associated with structural alterations of the AIS that are likely to have an impact on normal neuronal activity, which might contribute to neuronal dysfunction in AD.
PB Springer Nature
SN 2045-2322
YR 2022
FD 2022-05-24
LK https://hdl.handle.net/20.500.14352/123806
UL https://hdl.handle.net/20.500.14352/123806
LA eng
NO Antón-Fernández, A., León-Espinosa, G., DeFelipe, J., & Muñoz, A. (2022). Pyramidal cell axon initial segment in Alzheimer´s disease. Scientific Reports, 12(1). https://doi.org/10.1038/S41598-022-12700-9
NO This work was supported by grants from the following entities: PGC2018-094307-B-I00 from the Spanish “Ministerio de Ciencia e Innovación”; Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0066, Spain); Interdisciplinary Platform Cajal Blue Brain (CSIC, Spain); and a grant from the Alzheimer’s Association (ZEN-15-321663).
NO Ministerio de Ciencia e Innovación (España)
NO Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (España)
NO European Commission
NO Cajal Blue Brain Platform (España)
NO Alzheimer's Association
DS Docta Complutense
RD 20 ene 2026