title: From tau phosphorylation to tau aggregation: what about neuronal death?
abstract: Tau pathology is characterized by intracellular aggregates of abnormally and hyperphosphorylated tau proteins. It is encountered in many neurodegenerative disorders, but also in aging. These neurodegenerative disorders are referred to as tauopathies. Comparative biochemistry of the tau aggregates shows that they differ in both tau isoform phosphorylation and content, which enables a molecular classification of tauopathies. In conditions of dementia, NFD (neurofibrillary degeneration) severity is correlated to cognitive impairment and is often considered as neuronal death. Using tau animal models, analysis of the kinetics of tau phosphorylation, aggregation and neuronal death in parallel to electrophysiological and behavioural parameters indicates a disconnection between cognition deficits and neuronal cell death. Tau phosphorylation and aggregation are early events followed by cognitive impairment. Neuronal death is not observed before the oldest ages. A sequence of events may be the formation of toxic phosphorylated tau species, their aggregation, the formation of neurofibrillary tangles (from pre-tangles to ghost tangles) and finally neuronal cell death. This sequence will last from 15 to 25 years and one can ask whether the aggregation of toxic phosphorylated tau species is a protection against cell death. Apoptosis takes 24 h, but NFD lasts for 24 years to finally kill the neuron or rather to protect it for more than 20 years. Altogether, these data suggest that NFD is a transient state before neuronal death and that therapeutic interventions are possible at that stage.
authors.affiliation: Inserm, U837, rue Polonovski, 59045 Lille, France. luc.buee@inserm.fr
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Troquier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Burnouf
authors.forename: Karim
authors.initials: K
authors.lastname: Belarbi
authors.forename: Anneke
authors.initials: A
authors.lastname: Van der Jeugd
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmed
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernandez-Gomez
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Caillierez
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Grosjean
authors.forename: Séverine
authors.initials: S
authors.lastname: Begard
authors.forename: Bérangère
authors.initials: B
authors.lastname: Barbot
authors.forename: Dominique
authors.initials: D
authors.lastname: Demeyer
authors.forename: Hélène
authors.initials: H
authors.lastname: Obriot
authors.forename: Ingrid
authors.initials: I
authors.lastname: Brion
authors.forename: Valérie
authors.initials: V
authors.lastname: Buée-Scherrer
authors.forename: Claude-Alain
authors.initials: CA
authors.lastname: Maurage
authors.forename: Detlef
authors.initials: D
authors.lastname: Balschun
authors.forename: Rudi
authors.initials: R
authors.lastname: D'hooge
authors.forename: Malika
authors.initials: M
authors.lastname: Hamdane
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D011232:Chemical Precipitation; D004195:Disease Models, Animal; D006801:Humans; D008954:Models, Biological; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D055503:Protein Multimerization / Q000502:physiology*; D024801:Tauopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
chemical_list: D016875:tau Proteins; D011494:Protein Kinases