Detection of single amyloid beta-protein aggregates in the cerebrospinal fluid of Alzheimer's patients by fluorescence correlation spectroscopy

Nat Med. 1998 Jul;4(7):832-4. doi: 10.1038/nm0798-832.


Alzheimer's disease is associated with the intraparenchymal growth of plaque-like amyloid deposits. Amyloid plaques are formed by the progressive deposition and transformation of soluble amyloid beta-protein monomers into insoluble and fibrillar aggregates that contain amyloid beta-protein in a beta-pleated sheet conformation. This process is described as 'seeded polymerization' of the monomers with slow-nucleation and fast-growth kinetics. Soluble amyloid beta-protein monomers are present in the cortical extracellular space and in the cerebrospinal fluid, whereas insoluble aggregates so far can be found only by the examination of brain tissue by biopsy or autopsy. Here we present a biophysical method that uses the principle of seeded polymerization in combination with fluorescence correlation spectroscopy, which allowed us to detect single amyloid beta-peptide aggregates in the cerebrospinal fluid samples from Alzheimer's patients. All of 15 Alzheimer's samples but none of the 19 age-matched control samples produced large peaks with fluorescence correlation spectroscopy indicating the rapid aggregation of the fluorescent labelled synthetic amyloid beta-protein probe onto the amyloid beta-protein 'seeds' present in the cerebrospinal fluid. Our method could enable easy in vivo detection of the cerebral amyloid beta-protein pathology of Alzheimer's disease and might be of potential value to facilitate its routine diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Humans
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Spectrometry, Fluorescence


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)