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Human cerebrospinal fluid 6E10-immunoreactive protein species contain amyloid precursor protein fragments.

Artikel i vetenskaplig tidskrift
Författare Marianne K O Grant
Maureen Handoko
Malgorzata Rozga
Gunnar Brinkmalm
Erik Portelius
Kaj Blennow
Karen H Ashe
Kathleen R Zahs
Peng Liu
Publicerad i PloS one
Volym 14
Nummer/häfte 2
Sidor e0212815
ISSN 1932-6203
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor e0212815
Språk en
Länkar dx.doi.org/10.1371/journal.pone.021...
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Aged, Aged, 80 and over, Alzheimer Disease, cerebrospinal fluid, diagnosis, Amino Acid Sequence, Amyloid beta-Peptides, cerebrospinal fluid, chemistry, immunology, Biomarkers, cerebrospinal fluid, Blotting, Western, Disease Progression, Female, Humans, Immunoprecipitation, Male, Mass Spectrometry, Middle Aged, Molecular Weight, Peptide Fragments, cerebrospinal fluid, chemistry, immunology
Ämneskategorier Neurokemi

Sammanfattning

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 Aβ1-40/42 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.

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