Apolipoprotein L1 is increased in frontotemporal lobar degeneration post-mortem brain but not in ante-mortem cerebrospinal fluid

Hok‐A‐Hin, Yanaika S.; Dijkstra, Anke A.; Rábano, Alberto; Hoozemans, Jeroen J.M.; Castillo, L.; Seelaar, Harro; Swieten, John C. van; Pijnenburg, Yolande A.L.; Teunissen, Charlotte E.; Campo, Marta Del

doi:10.1016/j.nbd.2022.105813

Cited by 3 publications

(4 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on our previous experience, the period for developing and validating other in‐house immunoassays for biomarker candidates coming from MS proteomics studies (e.g., CSF APOL1) was, over 6 months. 48 We observed that THOP1 concentrations strongly correlated across the different THOP1 immunoassays, suggesting that the different antibody‐based platforms are likely detecting similar protein isoforms. Noteworthy, the comparison between our in‐house immunoassays showed some outliers on the Simoa platform, which could indicate that the assay still requires additional optimization (e.g., higher sample dilution, or longer antibody incubation times).…”

Section: Discussionmentioning

confidence: 74%

“…Both THOP1‐specific immunoassays were developed within 4–6 weeks. Based on our previous experience, the period for developing and validating other in‐house immunoassays for biomarker candidates coming from MS proteomics studies (e.g., CSF APOL1) was, over 6 months 48 . We observed that THOP1 concentrations strongly correlated across the different THOP1 immunoassays, suggesting that the different antibody‐based platforms are likely detecting similar protein isoforms.…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Thimet oligopeptidase as a potential CSF biomarker for Alzheimer's disease: A cross‐platform validation study

Hok‐A‐Hin

Bolsewig

Ruiters

et al. 2023

Alz & Dem Diag Ass & Dis Mo

Self Cite

View full text Add to dashboard Cite

INTRODUCTIONOur previous antibody‐based cerebrospinal fluid (CSF) proteomics study showed that Thimet oligopeptidase (THOP1), an amyloid beta (Aβ) neuropeptidase, was increased in mild cognitive impairment with amyloid pathology (MCI‐Aβ+) and Alzheimer's disease (AD) dementia compared with controls and dementia with Lewy bodies (DLB), highlighting the potential of CSF THOP1 as an early specific biomarker for AD. We aimed to develop THOP1 immunoassays for large‐scale analysis and validate our proteomics findings in two independent cohorts.METHODSWe developed in‐house CSF THOP1 immunoassays on automated Ella and Simoa platforms. The performance of the different assays were compared using Passing–Bablok regression analysis in a subset of CSF samples from the discovery cohort (n = 72). Clinical validation was performed in two independent cohorts (cohort 1: n = 200; cohort 2: n = 165) using the Ella platform.RESULTSTHOP1 concentrations moderately correlated between proteomics analysis and our novel assays (Rho > 0.580). In both validation cohorts, CSF THOP1 was increased in MCI‐Aβ+ (>1.3‐fold) and AD (>1.2‐fold) compared with controls; and between MCI‐Aβ+ and DLB (>1.2‐fold). Higher THOP1 concentrations were detected in AD compared with DLB only when both cohorts were analyzed together. In both cohorts, THOP1 correlated with CSF total tau (t‐tau), phosphorylated tau (p‐tau), and Aβ40 (Rho > 0.540) but not Aβ42.DISCUSSIONValidation of our proteomics findings underpins the potential of CSF THOP1 as an early specific biomarker associated with AD pathology. The use of antibody‐based platforms in both the discovery and validation phases facilitated the translation of proteomics findings, providing an additional workflow that may accelerate the development of biofluid‐based biomarkers.

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 92%

Thimet oligopeptidase as a potential CSF biomarker for Alzheimer's disease: A cross‐platform validation study

Hok‐A‐Hin

Bolsewig

Ruiters

et al. 2023

Alz & Dem Diag Ass & Dis Mo

Self Cite

View full text Add to dashboard Cite

show abstract

“…CLU and apolipoprotein E (APOE) are also instrumental in transferring long chain saturated lipids produced in reactive astrocytes to neurons, where they modulate neuronal survival and mediate astrocyte-induced toxicity after CNS injury and disease [ 60 ]. Apolipoprotein L1 (APOL1) is found in the CSF of patients affected by frontotemporal lobe dementia [ 61 ], and in our samples it was present only in CS. Apolipoprotein D (APOD), present in at least one sample of all tumors, increases upon brain aging and neurodegeneration, and it acts by controlling the redox state of cellular and extracellular lipid structures.…”

Section: Discussionmentioning

confidence: 93%

Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors

Magrassi

Brambilla

Viganò

et al. 2023

Cancers

View full text Add to dashboard Cite

Cystic formation in human primary brain tumors is a relatively rare event whose incidence varies widely according to the histotype of the tumor. Composition of the cystic fluid has mostly been characterized in samples collected at the time of tumor resection and no indications of the evolution of cystic content are available. We characterized the evolution of the proteome of cystic fluid using a bottom-up proteomic approach on sequential samples obtained from secretory meningioma (SM), cystic schwannoma (CS) and cystic high-grade glioma (CG). We identified 1008 different proteins; 74 of these proteins were found at least once in the cystic fluid of all tumors. The most abundant proteins common to all tumors studied derived from plasma, with the exception of prostaglandin D2 synthase, which is a marker of cerebrospinal fluid origin. Overall, the protein composition of cystic fluid obtained at different times from the same tumor remained stable. After the identification of differentially expressed proteins (DEPs) and the protein–protein interaction network analysis, we identified the presence of tumor-specific pathways that may help to characterize tumor–host interactions. Our results suggest that plasma proteins leaking from local blood–brain barrier disruption are important contributors to cyst fluid formation, but cerebrospinal fluid (CSF) and the tumor itself also contribute to the cystic fluid proteome and, in some cases, as with immunoglobulin G, shows tumor-specific variations that cannot be simply explained by differences in vessel permeability or blood contamination.

show abstract

“…It is associated with neurological diseases such as frontotemporal dementia and schizophrenia. APOL1 is increased in FTD [134,135]. The former is also associated with cholesterol alterations [136]; however, the pathogenesis involved in neural disease is unknown.…”

Section: Brain Expression Of Fam20c Targets-interactorsmentioning

confidence: 99%

Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis

Palma-Lara,

García Alonso-Themann,

Pérez-Durán

et al. 2023

IJMS

View full text Add to dashboard Cite

FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS.

show abstract

Apolipoprotein L1 is increased in frontotemporal lobar degeneration post-mortem brain but not in ante-mortem cerebrospinal fluid

Cited by 3 publications

References 58 publications

Thimet oligopeptidase as a potential CSF biomarker for Alzheimer's disease: A cross‐platform validation study

Thimet oligopeptidase as a potential CSF biomarker for Alzheimer's disease: A cross‐platform validation study

Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors

Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis

Contact Info

Product

Resources

About