title: Long-term in vivo imaging of fibrillar tau in the retina of P301S transgenic mice.
abstract: Tauopathies are widespread neurodegenerative disorders characterised by the intracellular accumulation of hyperphosphorylated tau. Especially in Alzheimer's disease, pathological alterations in the retina are discussed as potential biomarkers to improve early diagnosis of the disease. Using mice expressing human mutant P301S tau, we demonstrate for the first time a straightforward optical approach for the in vivo detection of fibrillar tau in the retina. Longitudinal examinations of individual animals revealed the fate of single cells containing fibrillar tau and the progression of tau pathology over several months. This technique is most suitable to monitor therapeutic interventions aimed at reducing the accumulation of fibrillar tau. In order to evaluate if this approach can be translated to human diagnosis, we tried to detect fibrillar protein aggregates in the post-mortem retinas of patients that had suffered from Alzheimer's disease or Progressive Supranuclear Palsy. Even though we could detect hyperphosphorylated tau, we did not observe any fibrillar tau or Aß aggregates. In contradiction to previous studies, our observations do not support the notion that Aβ or tau in the retina are of diagnostic value in Alzheimer's disease.
authors.affiliation: Department of Translational Brain Research, DZNE - German Centre for Neurodegenerative Diseases, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schön
authors.forename: Nadine A
authors.initials: NA
authors.lastname: Hoffmann
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ochs
authors.forename: Steffen
authors.initials: S
authors.lastname: Burgold
authors.forename: Severin
authors.initials: S
authors.lastname: Filser
authors.forename: Sonja
authors.initials: S
authors.lastname: Steinbach
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Seeliger
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Boris
authors.initials: B
authors.lastname: Schmidt
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008875:Middle Aged; D010766:Phosphorylation; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins