A novel fluorescent method for direct visualization of neurofibrillary pathology in Alzheimer's disease

Anyang Sun, Xuan V. Nguyen, Guoying Bing

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Methods currently available for detecting neurofibrillary pathology are indirect and depend on staining with exogenous chemicals or antibodies. In the present study, we report a novel method named intrinsic fluorescence induction (IFI), which allows direct visualization of neurofibrillary tangles (NFTs), neuropil threads (NTs), and neuritic plaques (NPs) in tissue sections of Alzheimer's disease (AD) brain. The IFI method is based on both induction of a red intrinsic fluorescence and quenching red background autofluorescence. The IFI procedure includes sustained hydrophobic treatment, protein secondary structure enhancement and incubation in high concentration of phosphate buffer. Following this procedure, a unique red fluorescence is generated from the structures of NFTs, NTs, and NPs in brain sections from AD patients. Sequential application of mild permanganate oxidation and 1% sodium borohydride selectively removes the red background autofluorescence, while the latter enhances the intrinsic fluorescence of neurofibrillary pathology. Comparative studies reveal that the IFI method is as sensitive as Gallyas silver staining, and more sensitive than Bielschowsky silver staining or PHF-1 immunostaining in detecting NFTs in the pre-α layer of entorhinal cortex and the pri-α layer of the entorhinal/transentorhinal cortex. Furthermore, the IFI method is sensitive in displaying plaque neurites and threads, but not NFTs in the hippocampus. This novel finding provides a direct method for detecting neurofibrillary pathology in particular regions of AD brain and a novel tool for AD research.

Original languageEnglish
Pages (from-to)17-27
Number of pages11
JournalJournal of Neuroscience Methods
Issue number1
StatePublished - 2001

Bibliographical note

Funding Information:
Human brain sections used in this study were kindly provided by the University of Kentucky Alzheimer's Disease Research Center headed by Dr William R. Markesbery. The authors gratefully acknowledge Dr Peter Davies for providing PHF-1 antibody. This work was supported by NIH grant 3R01 NS39345-01.


  • Alzheimer's disease
  • Fluorescence microscopy
  • Neuritic plaques
  • Neurofibrillary tangles
  • Neuropil threads
  • Silver staining

ASJC Scopus subject areas

  • Neuroscience (all)


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