Relationships among the cerebral amyloid peptides and their precursors.
Alzheimer's disease is characterized by deposits of amyloid in cerebral blood vessels and neuropil. Qualitative analyses of partially purified preparations of these amyloid deposits revealed the presence of a unique polypeptide now often called "beta peptide". This peptide is 40 residues long and it exhibits some amino terminal heterogeneity, which may result from the isolation procedure. The major amyloid peptide comprises at least 30% of the dry mass and 70% of the protein of washed neuritic plaque cores. These results indicate that the major peptide is the predominant proteinaceous component of cores; furthermore, they demonstrate that although cores may contain other substances such as aluminum silicate, polysaccharides, and lipids, amyloid peptide is a major component. More careful analysis reveals that the core amyloid peptide differs significantly from cerebrovascular amyloid peptide. Although the core amyloid peptide is constructed of the same backbone as the cerebrovascular amyloid peptide, it contains modifications that render the amino terminal region uncleavable by Edman degradation or by trypsin. It is unknown whether the lower solubility of core amyloid is related to these modifications. The original impetus for characterizing the differences between the core and cerebrovascular amyloid peptides arose from the question of whether both amyloid peptides were formed by a sequential pathway. Our results showing that core amyloid peptide is more extensively modified than vascular amyloid leads us to conclude that if a sequential pathway exists, vascular amyloid peptide must precede core amyloid peptide. Nevertheless, the discovery that amyloid precursor mRNA is widely and abundantly distributed throughout most tissues tends to discourage such a simple account of the relationship between these forms of amyloid.(ABSTRACT TRUNCATED AT 250 WORDS)
Miller
D L
DL
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Currie
J R
JR
Iqbal
K
K
Potempska
A
A
Styles
J
J
D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002536:Cerebral Arteries / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009454:Neurofibrils / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D011956:Receptors, Cell Surface