Paired helical filaments (PHF) are abnormal fibrous structures found in human nerve cells and their processes. Ultrastructural studies of the proto-filaments that make up the PHF revealed that the individual proto-filaments have a different substructure from normal neurofilaments or any other known fibrous profiles. Studies using immunological and biochemical methods suggested that abnormally phosphorylated tau,
ubiquitin and neurofilament
peptides are part of the PHF. Deposits of
amyloid fibres in
Alzheimer's disease and
senile dementia of the Alzheimer type (AD/SDAT) are found in meningeal and brain vessels, choroid plexus and
neuritic plaques. In 1984 Glenner and Wong reported the sequence of a beta-
protein isolated from cerebrovascular
amyloid. We used the amino acid sequence of the cerebrovascular
amyloid protein to synthesize
oligonucleotide probes specific for the gene encoding this
amyloid protein. Screening of a human brain cDNA library allowed us to isolate a clone which encodes the
amyloid peptide. In situ hybridization studies and Southern blot analysis of
a DNA sample isolated from a human-mouse hybrid cell line indicated that the corresponding genomic sequences of this
cDNA clone are located on human chromosome 21. Using immunochemical and histochemical methods, we have identified the cells associated with the formation of the
amyloid fibres. With immunochemical and biochemical methods we and others also showed that the
protein constituting
amyloid in AD/SDAT is different from
amyloid in unconventional
slow virus diseases.