Cerebrospinal fluid proteomic profiling of individuals with mild cognitive impairment and suspected non-Alzheimer's disease pathophysiology.
Alzheimer's disease
biomarkers
cerebrospinal fluid
mild cognitive impairment
pathophysiology
proteomics
suspected non-Alzheimer's disease pathophysiology
tau
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
14 Jun 2022
14 Jun 2022
Historique:
revised:
06
04
2022
received:
27
05
2021
accepted:
12
05
2022
entrez:
14
6
2022
pubmed:
15
6
2022
medline:
15
6
2022
Statut:
aheadofprint
Résumé
Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker concept that encompasses individuals with neuronal injury but without amyloidosis. We aim to investigate the pathophysiology of SNAP, defined as abnormal tau without amyloidosis, in individuals with mild cognitive impairment (MCI) by cerebrospinal fluid (CSF) proteomics. Individuals were classified based on CSF amyloid beta (Aβ)1-42 (A) and phosphorylated tau (T), as cognitively normal A-T- (CN), MCI A-T+ (MCI-SNAP), and MCI A+T+ (MCI-AD). Proteomics analyses, Gene Ontology (GO), brain cell expression, and gene expression analyses in brain regions of interest were performed. A total of 96 proteins were decreased in MCI-SNAP compared to CN and MCI-AD. These proteins were enriched for extracellular matrix (ECM), hemostasis, immune system, protein processing/degradation, lipids, and synapse. Fifty-one percent were enriched for expression in the choroid plexus. The pathophysiology of MCI-SNAP (A-T+) is distinct from that of MCI-AD. Our findings highlight the need for a different treatment in MCI-SNAP compared to MCI-AD.
Sections du résumé
BACKGROUND
BACKGROUND
Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker concept that encompasses individuals with neuronal injury but without amyloidosis. We aim to investigate the pathophysiology of SNAP, defined as abnormal tau without amyloidosis, in individuals with mild cognitive impairment (MCI) by cerebrospinal fluid (CSF) proteomics.
METHODS
METHODS
Individuals were classified based on CSF amyloid beta (Aβ)1-42 (A) and phosphorylated tau (T), as cognitively normal A-T- (CN), MCI A-T+ (MCI-SNAP), and MCI A+T+ (MCI-AD). Proteomics analyses, Gene Ontology (GO), brain cell expression, and gene expression analyses in brain regions of interest were performed.
RESULTS
RESULTS
A total of 96 proteins were decreased in MCI-SNAP compared to CN and MCI-AD. These proteins were enriched for extracellular matrix (ECM), hemostasis, immune system, protein processing/degradation, lipids, and synapse. Fifty-one percent were enriched for expression in the choroid plexus.
CONCLUSION
CONCLUSIONS
The pathophysiology of MCI-SNAP (A-T+) is distinct from that of MCI-AD. Our findings highlight the need for a different treatment in MCI-SNAP compared to MCI-AD.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Memorabel program of ZonMw
ID : 733050502
Organisme : Innovative Medicines Initiative Joint Undertaking
ID : 115372
Organisme : European Union's Seventh Framework Program
ID : FP7/2007-2013
Organisme : European Commission within the 5th framework program
ID : QLRT-2001- 2455
Organisme : Department of Health of the Basque Government
ID : 17.0.1.08.12.0000.2.454.01.41142.001.H
Informations de copyright
© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
Jack CR, Jr., Albert MS, Knopman DS, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):257-262.
Jack CR, Jr., Bennett DA, Blennow K, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-562.
Jack CR, Jr., Knopman DS, Chetelat G, et al. Suspected non-Alzheimer disease pathophysiology-concept and controversy. Nat Rev Neurol. 2016;12(2):117-124.
Saint-Aubert L, Lemoine L, Chiotis K, Leuzy A, Rodriguez-Vieitez E, Nordberg A. Tau PET imaging: present and future directions. Mol Neurodegener. 2017;12(1):19
Weigand AJ, Bangen KJ, Thomas KR, et al. Is tau in the absence of amyloid on the Alzheimer's continuum? A study of discordant PET positivity. Brain Commun. 2020;2(1):fcz046.
Vos SJ, Verhey F, Frolich L, et al. Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage. Brain. 2015;138(Pt 5):1327-1338.
Dani M, Brooks DJ, Edison P. Suspected non-Alzheimer's pathology - Is it non-Alzheimer's or non-amyloid? Ageing Res Rev. 2017;36:20-31.
Wisse LEM, de Flores R, Xie L, et al. Pathological drivers of neurodegeneration in suspected non-Alzheimer's disease pathophysiology. Alzheimers Res Ther. 2021;13(1):100
Lowe VJ, Lundt ES, Albertson SM, et al. Neuroimaging correlates with neuropathologic schemes in neurodegenerative disease. Alzheimers Dement. 2019;15(7):927-939.
Vos SJB, Xiong C, Visser PJ, et al. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. The Lancet Neurology. 2013;12(10):957-965.
van Harten AC, Kester MI, Visser PJ, et al. Tau and p-tau as CSF biomarkers in dementia: a meta-analysis. Clin Chem Lab Med. 2011;49(3):353-366.
Tijms BM, Gobom J, Reus L, et al. Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics. Brain. 2020;143(12):3776-3792.
Bos I, Verhey FR, Ramakers I, et al. Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline. Alzheimers Res Ther. 2017;9(1):101.
Bos I, Vos S, Vandenberghe R, et al. The EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics. Alzheimers Res Ther. 2018;10(1):64.
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183-194.
Visser PJ, Reus LM, Gobom J, et al. Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer's disease [published correction appears in Mol Neurodegener. Mol Neurodegener 2022;17(1):27. Published 2022 Mar 28. https://doi.org/10.1186/s13024-022-00521-3
Aalten P, Ramakers IH, Biessels GJ, et al. The Dutch Parelsnoer Institute - Neurodegenerative diseases; methods, design and baseline results. BMC Neurol. 2014;14:254.
de Rojas I, Moreno-Grau S, Tesi N, et al. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. 2021;12(1):3417. Published 2021 Jun 7. https://doi.org/10.1038/s41467-021-22491-8
Ten Kate M, Redolfi A, Peira E, et al. MRI predictors of amyloid pathology: results from the EMIF-AD Multimodal Biomarker Discovery study. Alzheimers Res Ther. 2018;10(1):100.
Tijms BM, Willemse EAJ, Zwan MD, et al. Unbiased approach to counteract upward drift in cerebrospinal fluid amyloid-beta 1-42 analysis results. Clin Chem. 2018;64(3):576-585.
Mi H, Muruganujan A, Huang X, et al. Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0). Nat Protoc. 2019;14(3):703-721.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol. 1995;57:289-300.
Lewin A, Grieve IC. Grouping Gene Ontology terms to improve the assessment of gene set enrichment in microarray data. BMC Bioinformatics. 2006;7:426.
Mi H, Muruganujan A, Ebert D, Huang X, Thomas PD. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 2019;47(D1):D419-D426.
Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607-D613.
Bindea G, Mlecnik B, Hackl H, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25(8):1091-1093.
Zhang Y, Sloan SA, Clarke LE, et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron. 2016;89(1):37-53.
Pollak J, Rai KG, Funk CC, et al. Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy. PloS One. 2017;12(3):e0172884.
Vogels T, Leuzy A, Cicognola C, et al. Propagation of tau pathology: integrating insights from postmortem and in vivo studies. Biol Psychiatry. 2020;87(9):808-818.
Vogel JW, Iturria-Medina Y, Strandberg OT, et al. Spread of pathological tau proteins through communicating neurons in human Alzheimer's disease. Nat Commun. 2020;11(1):2612.
Mendonca CF, Kuras M, Nogueira FCS, et al. Proteomic signatures of brain regions affected by tau pathology in early and late stages of Alzheimer's disease. Neurobiol Dis. 2019;130:104509.
Zhu K, Wang X, Sun B, et al. Primary age-related tauopathy in human subcortical nuclei. Front Neurosci. 2019;13:529.
Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70(11):960-969.
Digma LA, Madsen JR, Reas ET, et al. Tau and atrophy: domain-specific relationships with cognition. Alzheimers Res Ther. 2019;11(1):65.
Lun MP, Monuki ES, Lehtinen MK. Development and functions of the choroid plexus - cerebrospinal fluid system. Nat Rev Neurosci. 2015;16(8):445-457.
Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012;489(7416):391-399.
Rouillard AD, Gundersen GW, Fernandez NF, et al. The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database (Oxford). 2016;2016:baw100.
Grote S, Prufer K, Kelso J, Dannemann M. ABAEnrichment: an R package to test for gene set expression enrichment in the adult and developing human brain. Bioinformatics. 2016;32(20):3201-3203.
Ogawa M, Fukuyama H, Ouchi Y, Yamauchi H, Kimura J. Altered energy metabolism in Alzheimer's disease. J Neurol Sci. 1996;139(1):78-82.
Park J, Baik SH, Mook-Jung I, Irimia D, Cho H. Mimicry of central-peripheral immunity in Alzheimer's disease and discovery of neurodegenerative roles in neutrophil. Front Immunol. 2019;10:2231.
Huang WJ, Zhang X, Chen WW. Role of oxidative stress in Alzheimer's disease. Biomed Rep. 2016;4(5):519-522.
Harris SS, Wolf F, De Strooper B, Busche MA. Tipping the scales: peptide-dependent dysregulation of neural circuit dynamics in Alzheimer's disease. Neuron. 2020;107(3):417-435.
Evans HT, Benetatos J, van Roijen M, Bodea LG, Gotz J. Decreased synthesis of ribosomal proteins in tauopathy revealed by non-canonical amino acid labelling. EMBO J. 2019;38(13):e101174.
Banerjee S, Ferdosh S, Ghosh AN, Barat C. Tau protein- induced sequestration of the eukaryotic ribosome: implications in neurodegenerative disease. Sci Rep. 2020;10(1):5225.
Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev. 2000;33(1):95-130.
Tadayon E, Pascual-Leone A, Press D, Santarnecchi E. Choroid plexus volume is associated with levels of CSF proteins: relevance for Alzheimer's and Parkinson's disease. Neurobiology of Aging. 2020;89:108-117.
Demeestere D, Libert C, Vandenbroucke RE. Therapeutic implications of the choroid plexus-cerebrospinal fluid interface in neuropsychiatric disorders. Brain Behav Immun. 2015;50:1-13.
Saul J, Hutchins E, Reiman R, et al. Global alterations to the choroid plexus blood-CSF barrier in amyotrophic lateral sclerosis. Acta Neuropathol Commun. 2020;8(1):92.
Turner CA, Thompson RC, Bunney WE, et al. Altered choroid plexus gene expression in major depressive disorder. Front Hum Neurosci. 2014;8:238.
González-Marrero I, Giménez-Llort L, Johanson CE, et al. Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer's disease. Front Cell Neurosci. 2015;9:17
Zhang X, Fu Z, Meng L, He M, Zhang Z. The early events that initiate beta-amyloid aggregation in Alzheimer's disease. Front Aging Neurosci. 2018;10:359.
Jin LW, Masliah E, Iimoto D, et al. Neurofibrillary tangle-associated alteration of stathmin in Alzheimer's disease. Neurobiol Aging. 1996;17(3):331-341.
Antonell A, Mansilla A, Rami L, et al. Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer's disease. J Alzheimers Dis. 2014;42(3):901-908.
Mattsson N, Insel PS, Palmqvist S, et al. Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer's disease. EMBO Mol Med. 2016;8(10):1184-1196.
Sandelius A, Portelius E, Kallen A, et al. Elevated CSF GAP-43 is Alzheimer's disease specific and associated with tau and amyloid pathology. Alzheimers Dement. 2019;15(1):55-64.