Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer’s Disease

Jongbloed, Wesley; Dijk, Karin D. van; Mulder, Sandra D.; Berg, Wilma D. J. van de; Blankenstein, Marinus A.; Flier, Wiesje M. van der; Veerhuis, Robert

doi:10.3233/jad-150036

Cited by 55 publications

(44 citation statements)

References 31 publications

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“…We showed that clusterin was common to tears, AH and VH. This protein was recently demonstrated in VH as a potential biomarker of the AMD (59) and suspected to be a marker of Alzheimer disease in plasma (60). Cathepsin D, identified in the three different ocular fluids, was recently proposed as biomarker candidate in AH for neovascular AMD also (61).…”

Section: Discussionmentioning

confidence: 99%

Investigation of the global protein content from healthy human tears

Dor

Eperon

Lalive

et al. 2019

Experimental Eye Research

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Considering absence of invasiveness and side effects, tears emerge as a particularly attractive fluid for biomarker discovery and therefore for daily clinical use. However, to date, this fluid remains poorly studied in healthy condition. Here, we present an updated in-depth characterisation of the human healthy tear protein composition using proteomics approach. Both eyes of eight healthy controls were collected using the Schirmer's strip method. After liquid digestion and off-gel electrophoresis fractionation, three independent proteomics analyses were performed. Resulting files were searched against the uniprot_swissprot database (2017_05_10) using Thermo Proteome Discoverer (version 2.2) and a false discovery rate of 1% was selected. Globally, 1351 proteins were identified with 2 unique peptides. More specifically, 39% of the lacrimal proteins were enzymes, with high numbers of dehydrogenases, phosphatases, kinases and ligases. Immunoglobulins, serpins and 14-3-3 domains proteins emerged also as abundant lacrimal proteins. Pathway analyses highlighted among others the glycolysis and the coagulation and complement cascades. Our study therefore complements the existing data on healthy tears proteome. Nevertheless, extensive studies for deeply and definitively characterise this promising fluid are required in the near future in order to be able to routinely use this fluid in clinics. A better understanding of its protein content will probably open new avenues in the biomarker discovery and clinical practice in the near future.

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Section: Discussionmentioning

confidence: 99%

Investigation of the global protein content from healthy human tears

Dor

Eperon

Lalive

et al. 2019

Experimental Eye Research

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“…On the other hand, it can also play a neurotoxic role by contributing to the formation of Aβ oligomers and by mediating Aβ toxicity through the activation of cytotoxic pathways [92]. Blood clusterin levels are increased in both AD and MCI subjects as compared to controls [93,94], and are associated with the risk of developing AD [95] even though these results were not supported by all groups (see [93] for a review). Moreover, higher clusterin levels predict faster progression of cognitive decline in MCI and AD subjects [94,95].…”

Section: Blood Lipoproteins and Lipids As Biomarkers Of Dementiamentioning

confidence: 99%

Biomarkers of dementia in obstructive sleep apnea

Baril

Carrier

Lafrenière

et al. 2018

Sleep Medicine Reviews

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Epidemiologic and mechanistic evidence is increasingly supporting the notion that obstructive sleep apnea is a risk factor for dementia. Hence, the identification of patients at risk of cognitive decline due to obstructive sleep apnea may significantly improve preventive strategies and treatment decision-making. Cerebrospinal fluid and blood biomarkers obtained through genomic, proteomic and metabolomic approaches are improving the ability to predict incident dementia. Therefore, fluid biomarkers have the potential to predict vulnerability to neurodegeneration in individuals with obstructive sleep apnea, as well as deepen our understanding of pathophysiological processes linking obstructive sleep apnea and dementia. Many fluid biomarkers linked to Alzheimer's disease and vascular dementia show abnormal levels in individuals with obstructive sleep apnea, suggesting that these conditions share common underlying mechanisms, including amyloid and tau protein neuropathology, inflammation, oxidative stress, and metabolic disturbances. Markers of these processes include amyloid-β, tau proteins, inflammatory cytokines, acute-phase proteins, antioxydants and oxidized products, homocysteine and clusterin (apolipoprotein J). Thus, these biomarkers may have the ability to identify adults with obstructive sleep apnea at high risk of dementia and provide an opportunity for therapeutic intervention. Large cohort studies are necessary to establish a specific fluid biomarker panel linking obstructive sleep apnea to dementia risk.

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“…Moreover, in the transgenic AD mouse model (APP/PS1), increased plasma clusterin level, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques were shown [40,41]. The recent finding is that increased plasma clusterin levels have been associated with increased risk of conversion to AD and the rate of cognitive decline [42]. Clusterin may have a role in Aβ aggregation and clearance [43,44], and at high concentrations, clusterin may prevent Aβ aggregation through its binding to Aβ.…”

Section: Plasma Markersmentioning

confidence: 98%

“…Several groups have indicated that t-TAU concentration in CSF of AD patients is significantly higher than control [15,16]. On the other hand, the attenuation of the amount of Aβ 42 in CSF has been noted due to accumulation in the brain [17]. Thus, decrease in level of Aβ 42 , increase in t-TAU and P-TAU have been utilized as CSF biomarkers contributing to the diagnosis of AD [18].…”

Section: Csf Markersmentioning

confidence: 99%

“…After running SDS-PAGE, we performed in-gel digestion with trypsin and analyzed the tryptic peptides by reverse-phase liquid chromatography coupled with MALDI TOF/TOF MS spectrometry and performed database analysis for peptide sequencing. From this proteomic approach, about 240 types of proteins were indicated to be increased in the Aβ 42 -treated sample, compared with the control, suggesting that they were upregulated by Aβ 42 . From among these proteins, we focused on annexin A5, one of the annexin family proteins that commonly bind Ca 2+ and phospholipid.…”

Section: Another Plasma Biomarker Studymentioning

confidence: 99%

See 1 more Smart Citation

Plasma Biomarkers in Alzheimer’s Disease

Sohma¹,

Kokai²

2016

Update on Dementia

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Biomarker study on dementia has developed widely. In applying biomarkers, there seems to be several utilizations such as presymptomatic-and early-stage detection, differential diagnosis, and evaluation of treatment effect. Currently, most reliable fluid markers are amyloid peptide (Aβ) with microtubule-associated protein tau (TAU) and phosphorylated TAU (P-TAU) detected in cerebrospinal fluid (CSF). Aβ 42 correlates with plaque pathology, TAU reflects the intensity of neuroaxonal degeneration, and P-TAU may correlate with neurofibrillary tangle (NFT) pathology. An attenuation of the level of Aβ 42 and elevation in the ratio of Aβ 42 relative to the shorter major species of Aβ 42 peptide with 40 amino acid residues (Aβ 40 ) has been identified as significant events in the early stage of Alzheimer's disease (AD) pathology. In addition, there is great interest in blood-based markers of AD since blood extraction is much less invasive. Moreover, plasma biomarkers can be measured at relatively low expense once a standard system of measurement is established. Although there is not yet an established or validated diagnostic test for plasma biomarkers, there is great interest in bloodbased markers. We will summarize reported biomarkers, describe our novel potential plasma biomarker for AD (annexin A5), offering a strategy for selecting candidates, and show our results and evaluation.

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Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer’s Disease

Cited by 55 publications

References 31 publications

Investigation of the global protein content from healthy human tears

Investigation of the global protein content from healthy human tears

Biomarkers of dementia in obstructive sleep apnea

Plasma Biomarkers in Alzheimer’s Disease

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