12
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Neurofilament light chain in the vitreous humor of the eye

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E ( APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases.

          Methods

          This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5–1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (Aβ), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins, APOE genotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases.

          Results

          NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease ( p > 0.05). NfL levels were positively associated with increased vitreous levels of Aβ 40 ( p = 7.7 × 10 −5), Aβ 42 ( p = 2.8 × 10 −4), and t-tau ( p = 5.5 × 10 −7), but not with p-tau181 ( p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15, p = 5.3 × 10 −4), IL-16 ( p = 2.2 × 10 −4), monocyte chemoattractant protein-1 (MCP1, p = 4.1 × 10 −4), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1, p = 2.9 × 10 −6), Vegf-C ( p = 8.6 × 10 −6), vascular cell adhesion molecule-1 (VCAM-1, p = 5.0 × 10 −4), Tie-2 ( p = 6.3 × 10 −4), and intracellular adhesion molecular-1 (ICAM-1, p = 1.6 × 10 −4).

          Conclusion

          NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients’ clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.

          Related collections

          Most cited references77

          • Record: found
          • Abstract: found
          • Article: not found

          Ageing as a risk factor for neurodegenerative disease

          Ageing is the primary risk factor for most neurodegenerative diseases, including Alzheimer disease (AD) and Parkinson disease (PD). One in ten individuals aged ≥65 years has AD and its prevalence continues to increase with increasing age. Few or no effective treatments are available for ageing-related neurodegenerative diseases, which tend to progress in an irreversible manner and are associated with large socioeconomic and personal costs. This Review discusses the pathogenesis of AD, PD and other neurodegenerative diseases, and describes their associations with the nine biological hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing, stem cell exhaustion and altered intercellular communication. The central biological mechanisms of ageing and their potential as targets of novel therapies for neurodegenerative diseases are also discussed, with potential therapies including NAD+ precursors, mitophagy inducers and inhibitors of cellular senescence.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found

            Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts

            CSF and PET biomarkers of amyloid β and tau accurately detect Alzheimer's disease pathology, but the invasiveness, high cost, and poor availability of these detection methods restrict their widespread use as clinical diagnostic tools. CSF tau phosphorylated at threonine 181 (p-tau181) is a highly specific biomarker for Alzheimer's disease pathology. We aimed to assess whether blood p-tau181 could be used as a biomarker for Alzheimer's disease and for prediction of cognitive decline and hippocampal atrophy.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers

              Biomarkers have become an essential component of Alzheimer disease (AD) research and because of the pervasiveness of AD pathology in the elderly, the same biomarkers are used in cognitive aging research. A number of current issues suggest that an unbiased descriptive classification scheme for these biomarkers would be useful. We propose the “A/T/N” system in which 7 major AD biomarkers are divided into 3 binary categories based on the nature of the pathophysiology that each measures. “A” refers to the value of a β-amyloid biomarker (amyloid PET or CSF Aβ42); “T,” the value of a tau biomarker (CSF phospho tau, or tau PET); and “N,” biomarkers of neurodegeneration or neuronal injury ([18F]-fluorodeoxyglucose–PET, structural MRI, or CSF total tau). Each biomarker category is rated as positive or negative. An individual score might appear as A+/T+/N−, or A+/T−/N−, etc. The A/T/N system includes the new modality tau PET. It is agnostic to the temporal ordering of mechanisms underlying AD pathogenesis. It includes all individuals in any population regardless of the mix of biomarker findings and therefore is suited to population studies of cognitive aging. It does not specify disease labels and thus is not a diagnostic classification system. It is a descriptive system for categorizing multidomain biomarker findings at the individual person level in a format that is easy to understand and use. Given the present lack of consensus among AD specialists on terminology across the clinically normal to dementia spectrum, a biomarker classification scheme will have broadest acceptance if it is independent from any one clinically defined diagnostic scheme.
                Bookmark

                Author and article information

                Contributors
                Manju.Subramanian@bmc.org
                Journal
                Alzheimers Res Ther
                Alzheimers Res Ther
                Alzheimer's Research & Therapy
                BioMed Central (London )
                1758-9193
                17 September 2020
                17 September 2020
                2020
                : 12
                : 111
                Affiliations
                [1 ]GRID grid.475010.7, ISNI 0000 0004 0367 5222, Department of Ophthalmology, Boston Medical Center, , Boston University School of Medicine, ; 85 E Concord St. #8813, Boston, MA 02118 USA
                [2 ]GRID grid.475010.7, ISNI 0000 0004 0367 5222, Department of Medicine (Biomedical Genetics Section), , Boston University School of Medicine, ; Boston, MA USA
                [3 ]GRID grid.475010.7, ISNI 0000 0004 0367 5222, Department of Pharmacology and Experimental Therapeutics, , Boston University School of Medicine, ; Boston, MA USA
                [4 ]GRID grid.414326.6, ISNI 0000 0001 0626 1381, Geriatric Research Education and Clinical Center, , Bedford Veterans Affairs Medical Center, ; Bedford, MA USA
                [5 ]GRID grid.8761.8, ISNI 0000 0000 9919 9582, Department of Psychiatry and Neurochemistry at Institute of Neuroscience and Physiology, , Sahlgrenska Academy at University of Gothenburg, ; Gothenburg, Sweden
                [6 ]GRID grid.1649.a, ISNI 000000009445082X, Clinical Neurochemistry Laboratory, , Sahlgrenska University Hospital, ; Mölndal, Sweden
                [7 ]GRID grid.83440.3b, ISNI 0000000121901201, Department of Neurodegenerative Diseases, , UCL Institute of Neurology, ; London, UK
                [8 ]UK Dementia Research Institute at UCL, London, UK
                [9 ]GRID grid.8761.8, ISNI 0000 0000 9919 9582, Department of Clinical Neuroscience at Institute of Neuroscience and Physiology, , Sahlgrenska Academy at University of Gothenburg, ; Gothenburg, Sweden
                [10 ]GRID grid.185648.6, ISNI 0000 0001 2175 0319, Department of Ophthalmology, , University of Illinois at Chicago School of Medicine, ; Chicago, IL USA
                [11 ]GRID grid.475010.7, ISNI 0000 0004 0367 5222, Boston University Alzheimer’s Disease and CTE Center, , Boston University School of Medicine, ; Boston, MA USA
                [12 ]GRID grid.475010.7, ISNI 0000 0004 0367 5222, Department of Pathology and Laboratory Medicine, Boston Medical Center, , Boston University School of Medicine, ; Boston, MA USA
                [13 ]GRID grid.410370.1, ISNI 0000 0004 4657 1992, Department of Veterans Affairs Medical Center, , VA Boston Healthcare System, ; Boston, MA USA
                Author information
                http://orcid.org/0000-0002-0061-098X
                Article
                677
                10.1186/s13195-020-00677-4
                7500015
                32943089
                f046affb-7483-4d13-b4cb-81d8ce25c01b
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 15 June 2020
                : 1 September 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000049, National Institute on Aging;
                Award ID: R03AG063255
                Award ID: RF1AG054156
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000738, U.S. Department of Veterans Affairs;
                Award ID: I01-CX001038
                Funded by: FundRef http://dx.doi.org/10.13039/100010663, H2020 European Research Council;
                Award ID: (#681712
                Award Recipient :
                Funded by: Swedish Research Council
                Award ID: #2017-00915
                Award ID: #2018-02532
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Neurology
                alzheimer’s disease,vitreous humor,neuro-filament light chain,ocular biomarkers,amyloid beta,tau

                Comments

                Comment on this article