title: The influence of phospho-τ on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease.
abstract: The dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning and cognition. In the present study, we used intracellular injections of Lucifer yellow in fixed tissue to analyse over 19 500 dendritic spines that were completely reconstructed in three dimensions along the length of the basal dendrites of pyramidal neurons in the parahippocampal cortex and CA1 of patients with Alzheimer's disease. Following intracellular injection, sections were immunostained for anti-Lucifer yellow and with tau monoclonal antibodies AT8 and PHF-1, which recognize tau phosphorylated at Ser202/Thr205 and at Ser396/404, respectively. We observed that the diffuse accumulation of phospho-tau in a putative pre-tangle state did not induce changes in the dendrites of pyramidal neurons, whereas the presence of tau aggregates forming intraneuronal neurofibrillary tangles was associated with progressive alteration of dendritic spines (loss of dendritic spines and changes in their morphology) and dendrite atrophy, depending on the degree of tangle development. Thus, the presence of phospho-tau in neurons does not necessarily mean that they suffer severe and irreversible effects as thought previously but rather, the characteristic cognitive impairment in Alzheimer's disease is likely to depend on the relative number of neurons that have well developed tangles.
authors.affiliation: Laboratorio Cajal de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Campus Montegancedo S/N, 28223 Pozuelo de Alarcón, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Merino-Serrais
authors.forename: Ruth
authors.initials: R
authors.lastname: Benavides-Piccione
authors.forename: Lidia
authors.initials: L
authors.lastname: Blazquez-Llorca
authors.forename: Asta
authors.initials: A
authors.lastname: Kastanauskaite
authors.forename: Alberto
authors.initials: A
authors.lastname: Rábano
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.forename: Javier
authors.initials: J
authors.lastname: DeFelipe
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D049229:Dendritic Spines / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000502:physiology*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: 3D reconstruction; confocal microscopy; dendritic spine density and volume; hippocampal formation; intracellular injection