Open AccessHuman cerebrospinal fluid 6E10-immunoreactive protein species contain amyloid precursor protein fragments
Author(s) -
Marianne Grant,
Maureen Handoko,
Małgorzata Rózga,
Gunnar Brinkmalm,
Erik Portelius,
Kaj Blennow,
Karen H. Ashe,
Kathleen R. Zahs,
Peng Liu
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0212815
Subject(s) - immunoprecipitation , cerebrospinal fluid , amyloid precursor protein , blot , biology , microbiology and biotechnology , antibody , monoclonal antibody , amyloid (mycology) , alzheimer's disease , molecular mass , chemistry , biochemistry , disease , pathology , immunology , medicine , gene , enzyme , botany , neuroscience
In a previous study, we reported that levels of two types of protein species—a type of ~55-kDa species and a type of ~15-kDa species—are elevated in the lumbar cerebrospinal fluid (CSF) of cognitively intact elderly individuals who are at risk for Alzheimer’s disease (AD). These species are immunoreactive to the monoclonal antibody 6E10, which is directed against amino acids 6–10 of amyloid-β (Aβ), and their levels correlate with levels of total tau and tau phosphorylated at Thr181. In this study, we investigated the molecular composition of these AD-related proteins using immunoprecipitation (IP)/Western blotting coupled with IP/mass spectrometry. We show that canonical Aβ 1-40/42 peptides, together with amyloid-β precursor protein (APP) fragments located N-terminally of Aβ, are present in the ~55-kDa, 6E10-immunoreactive species. We demonstrate that APP fragments located N-terminally of Aβ, plus the N-terminal region of Aβ, are present in the ~15-kDa, 6E10-immunoreactive species. These findings add to the catalog of AD-related Aβ/APP species found in CSF and should motivate further study to determine whether these species may serve as biomarkers of disease progression.