title: Spatially pathogenic forms of tau detected in Alzheimer's disease brain tissue by fluorescence lifetime-based Förster resonance energy transfer.
abstract: In tauopathies including Alzheimer's disease (AD) tau molecules have lost their normal spatial distance to each other and appear in oligomeric or aggregated forms. Conventional immunostaining methods allow detection of abnormally phosphorylated or conformationally altered aggregated tau proteins, but fail to visualize oligomeric forms of tau. Here we show that tau molecules that lost their normal spatial localization can be detected on a subcellular level in postmortem central nervous system (CNS) tissue sections of AD patients by fluorescence lifetime-based Förster resonance energy transfer (FRET). Paraffin sections were co-immunostained with two tau-specific monoclonal antibodies recognizing the same epitope, but labeled with distinct fluorescence dyes suitable for spatial resolution at a nanometer scale by lifetime-based FRET. A FRET signal was detected in neuritic plaques and neurofibrillary tangles of CNS tissue sections of AD patients, showing associated tau proteins typically reflecting either fibrillary, oligomeric or aggregated tau. The 'pretangle-like' structures within the neuronal perikarya did not contain spatially pathogenic forms of tau accordingly to this method. Data demonstrate that fluorescence lifetime-based FRET can be applied to human brain tissue sections to detect pathogenic forms of tau molecules that lost their normal spatial distance.
authors.affiliation: Neural Regeneration Unit, Institute of Reconstructive Neurobiology, University Bonn and Hertie Foundation, University Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Sergey
authors.initials: S
authors.lastname: Larionov
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Wielgat
authors.forename: Yiner
authors.initials: Y
authors.lastname: Wang
authors.forename: Dietmar Rudolf
authors.initials: DR
authors.lastname: Thal
authors.forename: Harald
authors.initials: H
authors.lastname: Neumann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins