title: Biophysical and biochemical characterization of the intrinsic fluorescence from neurofibrillary tangles.
abstract: Recently, we developed a novel fluorescent method named intrinsic fluorescence induction that allows direct visualization of neurofibrillary pathology without introducing exogenous chromogens. In the present study, we further characterized the properties of this novel red fluorescence biophysically, biochemically, and neuropathologically. In vitro spectrofluorometry and in situ emission scan show that the intrinsic fluorescence of neurofibrillary tangles has a long emission wavelength peak at 620 nm and a large Stoke's shift of 70 nm. Dephosphorylation of Alzheimer's disease brain sections with alkaline phosphatase or denaturation with guanidine only causes a subtle reduction in the induced fluorescence of neurofibrillary tangles, while hydrofluoric acid or formic acid completely eliminates the fluorescence. Chemical modification of residue serine, but not tyrosine or tryptophan, reduced the intensity of induced fluorescence significantly. The induced fluorophore, thus, has unique properties, and its generation likely depends on the particular conformation of paired helical filaments, which may in turn depend on tau hyperphosphorylation.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536-0098, USA. gbing@uky.edu
authors.forename: Guoying
authors.initials: G
authors.lastname: Bing
authors.forename: Xuan V
authors.initials: XV
authors.lastname: Nguyen
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: William R
authors.initials: WR
authors.lastname: Markesbery
authors.forename: Anyang
authors.initials: A
authors.lastname: Sun
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D005453:Fluorescence; D019791:Guanidine / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D009419:Nerve Tissue Proteins / Q000172:deficiency; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000473:pathology*; D015513:Oncogene Proteins / Q000172:deficiency; D010766:Phosphorylation; D010777:Photochemistry; D011180:Postmortem Changes; D013050:Spectrometry, Fluorescence / Q000379:methods; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology
chemical_list: C428027:NREP protein, human; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D014357:Trypsin; D019791:Guanidine