PXD013451

PXD013451 is an original dataset announced via ProteomeXchange.

Title	Endo-Lysosomal Proteins and Ubiquitin CSF Concentrations in Alzheimer’s and Parkinson’s Disease
Description	Alzheimer’s (AD) and Parkinson’s disease (PD) are neurodegenerative disorders characterized by an accumulation of protein aggregates in the brain. AD is the most common cause of dementia and presents with impairment of memory and cognition. PD results from the loss of dopaminergic neurons which results in motor symptoms such as bradykinesia, rest tremor and/or rigidity. In AD and PD neuropathological investigation and genetic association indicate dysfunctional proteostasis as a pathological feature. Proteostasis is maintained by autophagy and the endosomal-lysosomal system and by the ubiquitin-proteasome system. We aimed to investigate new potential cerebrospinal fluid (CSF) biomarkers by targeting proteins involved in proteostasis. Measurable changes in protein concentrations in CSF might reflect altered proteostasis in neurodegenerative diseases. We identified and targeted 50 peptides from 18 proteins by combining solid-phase extraction (SPE) and parallel reaction monitoring mass spectrometry (PRM MS). The CSF concentration of these proteins were measured in four cross-sectional studies including subjects with AD (N = 61), PD (N = 21), prodromal AD (N = 10), stable mild cognitive impairment (stable MCI; N = 15), as well as controls (N = 68). Two pilot studies (Study 1 and 2) showed increased concentrations of several proteins in subjects with biochemical evidence of AD pathology compared to biochemically characterized normal subjects. A study (Study 3) including clinically characterized subjects instead showed decreased CSF concentration of several proteins in PD compared to prodromal AD. A follow up cohort (Study 4) was analyzed, also including clinically characterized subjects. Again decreased CSF concentrations were identified in PD compared to controls and AD. Proteins identified with significant different protein concentrations in the studies were AP2B1, C9, CTSB, CTSF, GM2A, LAMP1, LAMP2, TCN2, and ubiquitin. Proteins with repeatedly identified significant differences in concentration, in more than one study, were AP2B1, CTSB, CTSF, GM2A, and ubiquitin. No differences in CSF concentration of the investigated proteins were identified in clinically characterized cases with AD compared to controls suggesting if such differences exist, compared to PD, are minor. Further studies are need to investigate whether the promising protein candidates identified herein might serve as potential CSF biomarkers in PD.
HostingRepository	PanoramaPublic
AnnounceDate	2019-10-27
AnnouncementXML	Submission_2019-10-27_22:08:26.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Simon Sjödin
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-10 10:07:05	ID requested
⏵ 1	2019-10-27 22:08:27	announced

Sj, ö, din S, Brinkmalm G, Ö, hrfelt A, Parnetti L, Paciotti S, Hansson O, Hardy J, Blennow K, Zetterberg H, Brinkmalm A, Endo-lysosomal proteins and ubiquitin CSF concentrations in Alzheimer's and Parkinson's disease. Alzheimers Res Ther, 11(1):82(2019) [pubmed]

submitter keyword: Biomarker, CSF, Mass Spectrometry, Alzheimer’s disease, Parkinson’s disease

Henrik Zetterberg
contact affiliation	Department of Psychiatry and Neurochemistry, Inst. of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
contact email	henrik.zetterberg@clinchem.gu.se
lab head
Simon Sjödin
contact affiliation	Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
contact email	simon.sjodin@neuro.gu.se
dataset submitter

Panorama Public dataset URI