Comparison of methods for analysis of CSF proteins in patients with Alzheimer's disease.
Cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) and controls was analyzed by one- and two-dimensional gel electrophoresis, electron microscopy, and fluorescence microscopy with thioflavin S staining. In CSF from patients with AD, abnormal proteins were found following two-dimensional gel electrophoresis and silver staining. In CSF samples from most of the AD patients studied, a highly argentophilic material was detected upon silver staining the stacking gel of the one-dimensional gels. Electron microscopy of material eluted from the stacking gel showed fibers of approximately 7-10 nm diameter, with some twisting; properties consistent with paired helical filaments or amyloid. Furthermore, material with the characteristics of amyloid (fiber diameter ranging from 4-10 nm) was found in the CSF sediment. The CSF from AD patients had significantly elevated numbers of yellow fluorescent particles following thioflavin S staining when compared with age-matched, other neurological disease controls. We did not see an increase in autofluorescence, indicating that thioflavin S staining is specific. Our data suggest that AD CSF contains plaque amyloid and possibly proteins from neurofibrillary tangles. The thioflavin S staining method appears to have potential for development as a diagnostic tool.
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D052160:Benzothiazoles; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D008854:Microscopy, Electron; D008875:Middle Aged; D012834:Silver; D013844:Thiazoles
D052160:Benzothiazoles; D002556:Cerebrospinal Fluid Proteins; D013844:Thiazoles; C009462:thioflavin T; D012834:Silver