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

Marianne K.O. Grant, Maureen Handoko, Malgorzata Rozga, Gunnar Brinkmalm, Erik Portelius, Kaj Blennow, Karen H Ashe, Kathleen R Zahs, Peng Liu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0212815
JournalPloS one
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2019

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Cerebrospinal fluid
Amyloid beta-Protein Precursor
cerebrospinal fluid
amyloid
Cerebrospinal Fluid
Serum Amyloid A Protein
Alzheimer Disease
Immunoprecipitation
Alzheimer disease
Proteins
proteins
Amyloid
Disease Progression
Mass Spectrometry
Biomarkers
Western Blotting
Monoclonal Antibodies
Mass spectrometry
Amino Acids
Peptides

PubMed: MeSH publication types

  • Journal Article

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Grant, M. K. O., Handoko, M., Rozga, M., Brinkmalm, G., Portelius, E., Blennow, K., ... Liu, P. (2019). Human cerebrospinal fluid 6E10- immunoreactive protein species contain amyloid precursor protein fragments. PloS one, 14(2), [e0212815]. https://doi.org/10.1371/journal.pone.0212815

Human cerebrospinal fluid 6E10- immunoreactive protein species contain amyloid precursor protein fragments. / Grant, Marianne K.O.; Handoko, Maureen; Rozga, Malgorzata; Brinkmalm, Gunnar; Portelius, Erik; Blennow, Kaj; Ashe, Karen H; Zahs, Kathleen R; Liu, Peng.

In: PloS one, Vol. 14, No. 2, e0212815, 01.02.2019.

Research output: Contribution to journalArticle

Grant MKO, Handoko M, Rozga M, Brinkmalm G, Portelius E, Blennow K et al. Human cerebrospinal fluid 6E10- immunoreactive protein species contain amyloid precursor protein fragments. PloS one. 2019 Feb 1;14(2). e0212815. https://doi.org/10.1371/journal.pone.0212815
Grant, Marianne K.O. ; Handoko, Maureen ; Rozga, Malgorzata ; Brinkmalm, Gunnar ; Portelius, Erik ; Blennow, Kaj ; Ashe, Karen H ; Zahs, Kathleen R ; Liu, Peng. / Human cerebrospinal fluid 6E10- immunoreactive protein species contain amyloid precursor protein fragments. In: PloS one. 2019 ; Vol. 14, No. 2.
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