Avid binding of beta A amyloid peptide to its own precursor.
The senile plaque and congophilic angiopathy in brains of patients with Alzheimer's disease contain abnormal extracellular depositions. These depositions have very complex molecular structure, some elements of which have been identified. The most abundant protein in these structures is beta A amyloid peptide, which is produced by proteolytic processing of a larger protein, the amyloid precursor protein. It is not known how plaques and angiopathy are formed. Binding of proteins with the beta A peptide may be critical in this process. Using synthetic beta A peptides we show that the amyloid precursor protein found in cerebrospinal fluid binds beta A peptide with high avidity. Analysis of recombinant amyloid precursor proteins containing deletions of various domains demonstrate that the beta A peptide binds to the amino terminus of its own precursor. A model of plaque assembly is presented.
Strittmatter
W J
WJ
Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, North Carolina 27710.
Huang
D Y
DY
Bhasin
R
R
Roses
A D
AD
Goldgaber
D
D
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008567:Membranes, Artificial; D011994:Recombinant Proteins