Rapid Communication: Characterization of ?-Amyloid Peptide from Human Cerebrospinal Fluid

Autor: Ivan Lieberburg, Doris Lee, Dale Schenk, Pam S. Keim, Carmen Vigo-Pelfrey
Rok vydání: 1993
Předmět:
Zdroj: Journal of Neurochemistry. 61:1965-1968
ISSN: 1471-4159
0022-3042
DOI: 10.1111/j.1471-4159.1993.tb09841.x
Popis: β-Amyloid peptide (Aβ) is one of the main components of senile plaques in the brain tissue of Alzheimer's disease (AD) patients. Aβ 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. Aβ 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 Aβ may also be present in body fluids, such as CSF, that contact neurotic plaques. Recently using a specific enzyme-linked immunosorbent assay we were able to quantify one form of Aβ in CSF. In this report, using one of these antibodies covalently bound as an affinity matrix, multiple complex forms of Aβ have been isolated and characterized from CSF derived from patients with either meningitis or other neurological disorders. Amino acid sequencing reveals Aβ species with N-termini of Asp1, Glu3, His6, Glu11, and Val12, although on a molar basis, Asp1 represents the predominant amino-terminus. Laser desorption mass spectrometry confirmed the presence in CSF of Aβ species containing 27, 28, 30, 34, 35, 40, 42, and 43 amino acids, all beginning at Asp1; two stable trimmers, (Asp1-Met35).) and (His6-Ala42)3; and one stable dimer containing (Asp1-Val40)2. Some of these fragments have yet to be identified in brain either because they are generated solely in the CSF used in this study or because current procedures used to isolate brain amyloid result in their loss.
Databáze: OpenAIRE
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