Characterization of beta-amyloid peptide from human cerebrospinal fluid.
beta-Amyloid peptide (A beta) is one of the main components of senile plaques in the brain tissue of Alzheimer's disease (AD) patients. A beta is proteolytically cleaved from the amyloid precursor protein (APP), an integral membrane protein possessing a large extracellular N-terminal domain followed by a single membrane-spanning region and a short cytoplasmic C-terminal tail. A beta has been isolated from senile plaques and cerebral vascular tissue of AD brain and characterized as a heterogeneous peptide containing 28-43 amino acids whose sequence begins in the extracellular domain of APP and extends into the putative transmembrane sequence. It has long been speculated that A beta may also be present in body fluids, such as CSF, that contact neuritic plaques. Recently using a specific enzyme-linked immunosorbent assay we were able to quantify one form of A beta in CSF. In this report, using one of these antibodies covalently bound as an affinity matrix, multiple complex forms of A beta have been isolated and characterized from CSF derived from patients with either meningitis or other neurological disorders. Amino acid sequencing reveals A beta species with N-termini of Asp1, Glu3, His6, Glu11, and Val12, although on a molar basis, Asp1 represents the predominant aminoterminus. Laser desorption mass spectrometry confirmed the presence in CSF of A beta species containing 27, 28, 30, 34, 35, 40, 42, and 43 amino acids, all beginning at Asp1; two stable trimers, (Asp1-Met35)3 and (His6-Ala42)3; and one stable dimer containing (Asp1-Val40)2.(ABSTRACT TRUNCATED AT 250 WORDS)
Vigo-Pelfrey
C
C
Athena Neurosciences, Inc. South San Francisco, CA 94080.
Lee
D
D
Keim
P
P
Lieberburg
I
I
Schenk
D B
DB
D000328:Adult; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid* / Q000737:chemistry / Q000276:immunology; D000911:Antibodies, Monoclonal; D002648:Child; D002846:Chromatography, Affinity; D006801:Humans; D008581:Meningitis / Q000134:cerebrospinal fluid; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D010455:Peptides