title: Abnormal tau phosphorylation in the thorny excrescences of CA3 hippocampal neurons in patients with Alzheimer's disease.
abstract: A key symptom in the early stages of Alzheimer's disease (AD) is the loss of declarative memory. The anatomical substrate that supports this kind of memory involves the neural circuits of the medial temporal lobe, and in particular, of the hippocampal formation and adjacent cortex. A main feature of AD is the abnormal phosphorylation of the tau protein and the presence of tangles. The sequence of cellular changes related to tau phosphorylation and tangle formation has been studied with an antibody that binds to diffuse phosphotau (AT8). Moreover, another tau antibody (PHF-1) has been used to follow the pathway of neurofibrillary (tau aggregation) degeneration in AD. We have used a variety of quantitative immunocytochemical techniques and confocal microscopy to visualize and characterize neurons labeled with AT8 and PHF-1 antibodies. We present here the rather unexpected discovery that in AD, there is conspicuous abnormal phosphorylation of the tau protein in a selective subset of dendritic spines. We identified these spines as the typical thorny excrescences of hippocampal CA3 neurons in a pre-tangle state. Since thorny excrescences represent a major synaptic target of granule cell axons (mossy fibers), such aberrant phosphorylation may play an essential role in the memory impairment typical of AD patients.
authors.affiliation: Laboratorio de Circuitos Corticales (CTB), Universidad Politécnica de Madrid, Campus Montegancedo S/N, Pozuelo de Alarcón, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Blazquez-Llorca
authors.forename: Virginia
authors.initials: V
authors.lastname: Garcia-Marin
authors.forename: Paula
authors.initials: P
authors.lastname: Merino-Serrais
authors.forename: Jesús
authors.initials: J
authors.lastname: Ávila
authors.forename: Javier
authors.initials: J
authors.lastname: DeFelipe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000473:pathology; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; D055815:Young Adult; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D004268:DNA-Binding Proteins; C112309:PHF1 protein, human; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; D016875:tau Proteins