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Amyloid beta - An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid

ABSTRACT: Not available

INSTRUMENT(S): instrument model, LTQ FT Ultra

ORGANISM(S): Homo Sapiens (human) Felis Catus (cat) (felis Silvestris Catus)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Gunnar Brinkmalm

PROVIDER: PRD000651 | Pride | 2012-07-01

REPOSITORIES: Pride

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			Action	DRS
	PRIDE_Exp_Complete_Ac_21807.pride.mgf.gz	Mgf
	PRIDE_Exp_Complete_Ac_21807.pride.mztab.gz	Mztab
	PRIDE_Exp_Complete_Ac_21807.xml.gz	Xml
	PRIDE_Exp_Complete_Ac_21808.pride.mgf.gz	Mgf
	PRIDE_Exp_Complete_Ac_21808.pride.mztab.gz	Mztab

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Publications

An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid.

Brinkmalm Gunnar G Portelius Erik E Öhrfelt Annika A Mattsson Niklas N Persson Rita R Gustavsson Mikael K MK Vite Charles H CH Gobom Johan J Månsson Jan-Eric JE Nilsson Jonas J Halim Adnan A Larson Göran G Rüetschi Ulla U Zetterberg Henrik H Blennow Kaj K Brinkmalm Ann A

Journal of mass spectrometry : JMS 20120501 5

Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility ...[more]

PMID: 22576872

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

Project description: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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Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-β oligomerizes.

Project description:Pleiotropic roles are proposed for brain extracellular vesicles (EVs) in the development of Alzheimer's disease (AD). Our previous studies have suggested a beneficial role for EVs in AD, where the endosomal system in vulnerable neurons is compromised, contributing to the removal of accumulated material from neurons. However, the involvement of EVs in propagating AD amyloidosis throughout the brain has been considered because the amyloid-β precursor protein (APP), APP metabolites, and key APP cleaving enzymes were identified in association with EVs. Here, we undertook to determine whether the secretase machinery is actively processing APP in EVs isolated from the brains of wild-type and APP overexpressing Tg2576 mice. We found that full-length APP is cleaved in EVs incubated in the absence of cells. The resulting metabolites, both α- and β-APP carboxyl-terminal fragments and APP intracellular domain accumulate in EVs over time and amyloid-β dimerizes. Thus, EVs contribute to the removal from neurons and transport of APP-derived neurotoxic peptides. While this is potentially a venue for propagation of the pathology throughout the brain, it may contribute to efficient removal of neurotoxic peptides from the brain.

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