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 Nature Research YR 2022 FD 2022-05-24 LK https://hdl.handle.net/20.500.14352/87538 UL https://hdl.handle.net/20.500.14352/87538 LA eng NO Ministerio de Ciencia e Innovación (MICIN) NO Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED) NO Plataforma Interdisciplinar Cajal Blue Brain (CSIC, España) NO Asociación de Alzheimer DS Docta Complutense RD 19 abr 2025