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- Kawahara, R., et al.
(author)
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Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis
- 2021
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In: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 18, s. 1304-1316
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Journal article (peer-reviewed)abstract
- Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. This analysis presents the results of a community-based evaluation of existing software for large-scale glycopeptide data analysis.
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| 3. |
- Ally, M., et al.
(author)
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Cross-sectional and longitudinal evaluation of plasma glial fibrillary acidic protein to detect and predict clinical syndromes of Alzheimer's disease
- 2023
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In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - 2352-8729. ; 15:4
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Journal article (peer-reviewed)abstract
- Introduction: This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain (NfL), and phosphorylated tau (p-tau)181+231.Methods: Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross-sectional and longitudinal outcomes.Results: Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference = 0.90 standard deviation [SD]) and mild cognitive impairment (adjusted mean difference = 0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia.Discussion: Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD.
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| 4. |
- Morrison, M. S., et al.
(author)
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Ante-mortem plasma phosphorylated tau (181) predicts Alzheimer's disease neuropathology and regional tau at autopsy
- 2022
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:10, s. 3546-3557
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Journal article (peer-reviewed)abstract
- In one of the largest studies of its kind, Morrison et al. show that ante-mortem plasma phosphorylated-tau(181) concentrations accurately differentiate brain donors with and without autopsy-confirmed Alzheimer's disease. Blood tests could be a minimally invasive, cost-effective tool for the detection and monitoring of Alzheimer's disease. Blood-based biomarkers such as tau phosphorylated at threonine 181 (phosphorylated-tau(181)) represent an accessible, cost-effective and scalable approach for the in vivo detection of Alzheimer's disease pathophysiology. Plasma-pathological correlation studies are needed to validate plasma phosphorylated-tau(181) as an accurate and reliable biomarker of Alzheimer's disease neuropathological changes. This plasma-to-autopsy correlation study included participants from the Boston University Alzheimer's Disease Research Center who had a plasma sample analysed for phosphorylated-tau(181) between 2008 and 2018 and donated their brain for neuropathological examination. Plasma phosphorelated-tau(181) was measured with single molecule array technology. Of 103 participants, 62 (60.2%) had autopsy-confirmed Alzheimer's disease. Average time between blood draw and death was 5.6 years (standard deviation = 3.1 years). Multivariable analyses showed higher plasma phosphorylated-tau(181) concentrations were associated with increased odds for having autopsy-confirmed Alzheimer's disease [AUC = 0.82, OR = 1.07, 95% CI = 1.03-1.11, P < 0.01; phosphorylated-tau standardized (z-transformed): OR = 2.98, 95% CI = 1.50-5.93, P < 0.01]. Higher plasma phosphorylated-tau(181) levels were associated with increased odds for having a higher Braak stage (OR = 1.06, 95% CI = 1.02-1.09, P < 0.01) and more severe phosphorylated-tau across six cortical and subcortical brain regions (ORs = 1.03-1.06, P < 0.05). The association between plasma phosphorylated-tau(181) and Alzheimer's disease was strongest in those who were demented at time of blood draw (OR = 1.25, 95%CI = 1.02-1.53), but an effect existed among the non-demented (OR = 1.05, 95% CI = 1.01-1.10). There was higher discrimination accuracy for Alzheimer's disease when blood draw occurred in years closer to death; however, higher plasma phosphorylated-tau(181) levels were associated with Alzheimer's disease even when blood draw occurred >5 years from death. Ante-mortem plasma phosphorylated-tau(181) concentrations were associated with Alzheimer's disease neuropathology and accurately differentiated brain donors with and without autopsy-confirmed Alzheimer's disease. These findings support plasma phosphorylated-tau(181) as a scalable biomarker for the detection of Alzheimer's disease.
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- Ramirez, M. I., et al.
(author)
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Technical challenges of working with extracellular vesicles
- 2018
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 10:3, s. 881-906
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Journal article (peer-reviewed)abstract
- Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review. © 2018 The Royal Society of Chemistry.
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| 7. |
- Sugarman, M. A., et al.
(author)
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A longitudinal examination of plasma neurofilament light and total tau for the clinical detection and monitoring of Alzheimer's disease
- 2020
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 94, s. 60-70
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Journal article (peer-reviewed)abstract
- We examined baseline and longitudinal associations between plasma neurofilament light (NfL) and total tau (t-tau), and the clinical presentation of Alzheimer's disease (AD). A total of 579 participants (238, normal cognition [NC]; 185, mild cognitive impairment [MCI]; 156, AD dementia) had baseline blood draws; 82% had follow-up evaluations. Plasma samples were analyzed for NfL and t-tau using Simoa technology. Baseline plasma NfL was higher in AD dementia than MCI (standardized mean difference = 0.55, 95% CI: 0.37–0.73) and NC (standardized mean difference = 0.68, 95% CI: 0.49–0.88), corresponded to Clinical Dementia Rating scores (OR = 1.94, 95% CI: 1.35–2.79]), and correlated with all neuropsychological tests (r's = 0.13–0.42). Longitudinally, NfL did not predict diagnostic conversion but predicted decline on 3/10 neuropsychological tests. Baseline plasma t-tau was higher in AD dementia than NC with a small effect (standardized mean difference = 0.33, 95% CI: 0.10–0.57) but not MCI. t-tau did not statistically significant predict any longitudinal outcomes. Plasma NfL may be useful for the detection of AD dementia and monitoring of disease progression. In contrast, there was minimal evidence in support of plasma t-tau. © 2020 Elsevier Inc.
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| 8. |
- Chatterjee, S., et al.
(author)
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Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers
- 2019
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 19:21-22
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Journal article (peer-reviewed)abstract
- While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade. PMGs, particularly Man2‐3GlcNAc2Fuc1, are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0–50.2%). Analyses of paired (tumor/non‐tumor) and stage‐stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis.
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| 9. |
- Montoliu-Gaya, Laia, et al.
(author)
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Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.
- 2024
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In: Acta neuropathologica. - 1432-0533. ; 147:1
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Journal article (peer-reviewed)abstract
- Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD=69, non-AD=54) from the Boston University Alzheimer's disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195-205, 212-221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC=89.8), p-tau231 (AUC=83.4), and p-tau205 (AUC=81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR<1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217=15.29, ORp-tau205=5.05 and ORp-tau231=3.86) and Braak staging (ORp-tau217=14.29, ORp-tau205=5.27 and ORp-tau231=4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease.
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| 10. |
- Frank, Brandon, et al.
(author)
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Plasma p-tau181 shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.
- 2022
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:8, s. 1523-1536
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Journal article (peer-reviewed)abstract
- We examined the ability of plasma hyperphosphorylated tau (p-tau)181 to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL).Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables.Plasma p-tau181 discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau181 had a direct association with cognitive diagnosis in a bootstrapped GGM.These results support plasma p-tau181 for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.
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