title: Vulnerable neuronal subsets in Alzheimer's and Pick's disease are distinguished by their tau isoform distribution and phosphorylation.
abstract: Aggregated tau proteins constitute the basic matrix of neuronal inclusions specific to numerous neurodegenerative disorders. Monodimensional and two-dimensional Western blot analyses performed on cortical brain homogenates allowed discrimination between disease-specific tau protein profiles. These observations raised the issue of the physiopathological significance of such specificities. Alzheimer's disease (AD) pathological tau proteins (PTPs) (tau 74, 69, 64, 55) were compared with those of Pick's disease (PiD) (tau 64, 55) using a panel of antibodies against peptidic sequences of tau isoforms corresponding to exons 2, 3, and 10. AD and PiD could then be critically differentiated by the absence of translated tau isoforms with exon 10 in PiD PTPs, along with the absence of the phosphorylation site on Ser262. Immunohistochemical studies corroborate these findings. Indeed, Pick bodies were strongly immunostained by an anti-"exon 2" antibody but failed to reveal any anti-exon 10 reactive epitope. Tangles in AD contained exon 2, 3, and 10 epitopes. Altogether, our results demonstrated that Pick bodies develop within specific neuronal subsets that express specific patterns of 7 isoforms lacking exon 10 peptidic sequence. We conclude that neurodegenerative disorders imply attrition of selectively vulnerable neuronal subsets, a process revealed, and may be sustained by specific tau isoform patterns.
authors.affiliation: Unité INSERM 422, Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Delacourte
authors.forename: N
authors.initials: N
authors.lastname: Sergeant
authors.forename: A
authors.initials: A
authors.lastname: Wattez
authors.forename: D
authors.initials: D
authors.lastname: Gauvreau
authors.forename: Y
authors.initials: Y
authors.lastname: Robitaille
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D015153:Blotting, Western; D001923:Brain Chemistry; D003704:Dementia / Q000473:pathology*; D018604:Epitope Mapping; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007536:Isomerism; D009474:Neurons / Q000737:chemistry / Q000145:classification*; D016875:tau Proteins / Q000032:analysis*
chemical_list: D016875:tau Proteins