The presence of abundant intraneuronal
amyloid in the form of neurofibrillary tangles (NFT) in the brains of Guamanian
parkinsonism-
dementia patients and the absence of extraneuronal
amyloid in the form of vascular
amyloid deposits or
senile plaques permit the purification of NFT without contamination with extraneuronal
amyloid. Thus, we have isolated and determined the amino acid sequence of the
polypeptide subunit of the
amyloid fibrils of these NFT and describe their ultrastructure. The NFT, which consist of single and paired helical filaments, similar to those of
Alzheimer disease, and occasionally triple helical filaments, are composed of multimeric aggregates of a
polypeptide of 42
amino acids (A4
protein). The relative molecular mass of the
subunit protein, 4.0-4.5 kDa, is the same as the molecular mass of the
amyloid of NFT, of the
amyloid plaque cores, and of vascular
amyloid deposits in
Alzheimer disease and
Down syndrome; the sequence of 15
amino acid residues at the N-terminus of the
amyloid fibrils in the NFT of Guamanian
parkinsonism-
dementia is identical to that of the
amyloid of NFT,
amyloid plaque cores, and cerebrovascular deposits in
Alzheimer disease and
Down syndrome. Furthermore, the heterogeneity, or variation in
polypeptide length, of the N-terminus of the
amyloid of Guamanian
parkinsonism-
dementia is the same as in
Alzheimer disease and
Down syndrome. Our observations indicate that the brain amyloids of these diseases have a common
subunit protein, which would also indicate a common pathogenesis.