Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease.
The pathological findings of Alzheimer's disease include amyloid deposition in cerebral blood vessels and in senile plaques. Both deposits are known to include peptides that contain a common sequence. Both forms of amyloid were isolated and their peptide compositions were determined. The peptides were resolved by size-exclusion chromatography in 70% formic acid, and reverse-phase chromatography in 60% formic acid, 0-40% acetonitrile. Senile plaque amyloid cores contain about 25% protein, about 70% of which is composed of peptides containing the beta-amyloid sequence. Amino-terminal sequencing of the core amyloid peptides (CAPs) revealed extensive amino-terminal heterogeneity, with variable amounts of blocked amino termini. Matrix-assisted, laser-desorption-time-of-flight mass spectrometry of the CAP mixture revealed an array of peptides the molecular weights of which corresponded to peptides beginning with each of the first 11 amino acids of the beta-peptide sequence and ending with Ala-42 of that sequence. The carboxyl-terminal residues were identified by tandem mass spectrometry of chymotrypsin digests. CAP possessed a minor degree of carboxyl-terminal heterogeneity. Cerebrovascular amyloid peptides (CVAPs) possessed minor degrees of both amino- and carboxyl-terminal heterogeneity. The major CVAP commenced at Asp-1 and ended at Val-40. Minor components of CAP possessed masses of 8000-9000 Da and the same amino-terminal residues as the major components of CAP. They may be precursors to the smaller CAPs. The differences in amino termini and carboxyl termini of CAPs and CVAPs suggest that the two types of amyloid form by different pathways, on which they encounter different proteases.
Miller
D L
DL
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Papayannopoulos
I A
IA
Styles
J
J
Bobin
S A
SA
Lin
Y Y
YY
Biemann
K
K
Iqbal
K
K
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000682:Amyloid / Q000032:analysis* / Q000737:chemistry; D002196:Capillaries / Q000737:chemistry; D002540:Cerebral Cortex / Q000098:blood supply*; D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000032:analysis* / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000596:Amino Acids; D000682:Amyloid; D010446:Peptide Fragments; D010455:Peptides; D002918:Chymotrypsin