Cerebrospinal fluid profile of NPTX2 supports role of Alzheimer’s disease-related inhibitory circuit dysfunction in adults with Down syndrome
Open accessAbstract
Background: Alzheimer’s disease (AD) is the major cause of death in adults with Down syndrome (DS). There is an urgent need for objective markers of AD in the DS population to improve early diagnosis and monitor disease progression. NPTX2 has recently emerged as a promising cerebrospinal fluid (CSF) biomarker of Alzheimer-related inhibitory circuit dysfunction in sporadic AD patients. The objective of this study was to evaluate NPTX2 in the CSF of adults with DS and to explore the relationship of NPTX2 to CSF levels of the PV interneuron receptor, GluA4, and existing AD biomarkers (CSF and neuroimaging). Methods: This is a cross-sectional, retrospective study of adults with DS with asymptomatic AD (aDS, n = 49), prodromal AD (pDS, n = 18) and AD dementia (dDS, n = 27). Non-trisomic controls (n = 34) and patients with sporadic AD dementia (sAD, n = 40) were included for comparison. We compared group differences in CSF NPTX2 according to clinical diagnosis and degree of intellectual disability. We determined the relationship of CSF NPTX2 levels to age, cognitive performance (CAMCOG, free and cued selective reminding, semantic verbal fluency), CSF levels of a PV-interneuron marker (GluA4) and core AD biomarkers; CSF Aβ 1–42, CSF t-tau, cortical atrophy (magnetic resonance imaging) and glucose metabolism ([18 F]-fluorodeoxyglucose positron emission tomography). Results: Compared to controls, mean CSF NPTX2 levels were lower in DS at all AD stages; aDS (0.6-fold, adj.p < 0.0001), pDS (0.5-fold, adj.p < 0.0001) and dDS (0.3-fold, adj.p < 0.0001). This reduction was similar to that observed in sporadic AD (0.5-fold, adj.p < 0.0001). CSF NPTX2 levels were not associated with age (p = 0.6), intellectual disability (p = 0.7) or cognitive performance (all p > 0.07). Low CSF NPTX2 levels were associated with low GluA4 in all clinical groups; controls (r2 = 0.2, p = 0.003), adults with DS (r2 = 0.4, p < 0.0001) and sporadic AD (r2 = 0.4, p < 0.0001). In adults with DS, low CSF NPTX2 levels were associated with low CSF Aβ 1–42 (r2 > 0.3, p < 0.006), low CSF t-tau (r2 > 0.3, p < 0.001), increased cortical atrophy (p < 0.05) and reduced glucose metabolism (p < 0.05). Conclusions: Low levels of CSF NPTX2, a protein implicated in inhibitory circuit function, is common to sporadic and genetic forms of AD. CSF NPTX2 represents a promising CSF surrogate marker of early AD-related changes in adults with DS.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CSF NPTX2 levels assessed by Western Blot, in-house ELISA and mass spectrometry were decreased in both sporadic and genetic forms of MCI and AD dementia in comparison with cognitive healthy controls.
“CSF NPTX2 levels assessed by WB, in-house ELISA and mass spectrometry were decreased in both sporadic and genetic forms of MCI and AD dementia in comparison with cognitive healthy controls (Belbin et al. 2020; Galasko et al. 2019; Nilsson et al. 2021; Soldan et al. 2019; Xiao et al. 2017).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Belbin et al. 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Consensus Guidelines for CSF and Blood Biobanking for CNS Biomarker Studies
Teunissen, C. E., Tumani, H., Bennett, J. L., Berven, F. S., Brundin, L., Comabella, M., Franciotta, D. M., Federiksen, J. L., Fleming, J. O., Furlan, R., et al. (2011) · Multiple Sclerosis International · doi:10.1155/2011/246412 · Cited by 69 · see citing works
RetractedMcKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · see citing works
Measuring the thickness of the human cerebral cortex from magnetic resonance images
Fischl, B. R., & Dale, A. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.200033797 · Cited by 5,789 · see citing works
Clinical and biomarker changes in dominantly inherited Alzheimer's disease
Bateman, R. J., Xiong, C., Benzinger, T. L. S., Fagan, A. M., Goate, A., Fox, N. C., Marcus, D. S., Cairns, N. J., Xie, X., Blazey, T. M., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1202753 · Cited by 3,814 · see citing works
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Dubois, B., Feldman, H. H., Jacova, C., Hampel, H., Molinuevo, J. L., Blennow, K., DeKosky, S. T., Gauthier, S., Selkoe, D., Bateman, R., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70090-0 · Cited by 3,321 · see citing works
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644 · see citing works
Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome
Wisniewski, K. E., Wisniewski, H. M., & Wen, G. Y. (1985) · Annals of Neurology · doi:10.1002/ana.410170310 · Cited by 1,159 · see citing works
Choi, M., Chang, C.-Y., Clough, T., Broudy, D., Killeen, T., MacLean, B., & Olga Vitek, A. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu305 · Cited by 1,041 · see citing works
Network abnormalities and interneuron dysfunction in Alzheimer disease
Palop, J. J., & Mucke, L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.141 · Cited by 1,022 · see citing works
Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI
Landau, S. M., Harvey, D., Madison, C. M., Koeppe, R. A., Reiman, E. M., Foster, N. L., Weiner, M. W., & Jagust, W. J. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.07.002 · Cited by 750 · see citing works
Um, J. W., Kaufman, A. C., Kostylev, M., Heiss, J. K., Stagi, M., Takahashi, H., Kerrisk, M. E., Vortmeyer, A., Wisniewski, T., Koleske, A. J., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.036 · Cited by 572 · see citing works
Fuchs, E. C., Zivkovic, A. R., Cunningham, M. O., Middleton, S., LeBeau, F. E. N., Bannerman, D. M., Rozov, A., Whittington, M. A., Traub, R. D., Rawlins, J. N. P., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.031 · Cited by 532 · see citing works
High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotypingPreprint
Peiffer, D. A., Le, J. M., Steemers, F. J., Chang, W., Jenniges, T., Garcia, F., Haden, K., Li, J., Shaw, C. A., Belmont, J. W., et al. (2006) · Genome Research · doi:10.1101/gr.5402306 · Cited by 519 · see citing works
La Joie, R., Perrotin, A., Barré, L., Hommet, C., Mézenge, F., Ibazizene, M., Camus, V., Abbas, A., Landeau, B., Guilloteau, D., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.2170-12.2012 · Cited by 374 · see citing works
Fortea, J., Vilaplana, E., Carmona-Iragui, M., Benejam, B., Videla, L., Barroeta, I., Fernández, S., Altuna, M., Pegueroles, J., Montal, V., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30689-9 · Cited by 340 · see citing works
Self-citationNarp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons
Chang, M. C., Park, J. M., Pelkey, K. A., Grabenstatter, H. L., Xu, D., Linden, D. J., Sutula, T. P., McBain, C. J., & Worley, P. F. (2010) · Nature Neuroscience · doi:10.1038/nn.2621 · Cited by 316 · see citing works
Self-citationNPTX2 and cognitive dysfunction in Alzheimer’s Disease
Xiao, M.-F., Xu, D., Craig, M. T., Pelkey, K. A., Chien, C.-C., Shi, Y., Zhang, J., Resnick, S., Pletnikova, O., Salmon, D., et al. (2017) · eLife · doi:10.7554/elife.23798 · Cited by 316 · see citing works
Self-citationGreve, D. N., Salat, D. H., Bowen, S., Izquierdo‐Garcia, D., Schultz, A. P., Catana, C., Becker, J. A., Svarer, C., Knudsen, G. M., Sperling, R. A., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.02.042 · Cited by 312 · see citing works
Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data
Greve, D. N., Svarer, C., Fisher, P. M., Feng, L., Hansen, A. E., Baare, W., Rosen, B., Fischl, B., & Knudsen, G. M. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.12.021 · Cited by 264 · see citing works
Pelkey, K. A., Barksdale, E., Craig, M. T., Yuan, X., Sukumaran, M., Vargish, G. A., Mitchell, R. M., Wyeth, M. S., Petralia, R. S., Chittajallu, R., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.02.020 · Cited by 245 · see citing works
Self-citationLleó, A., Núñez-Llaves, R., Alcolea, D., Chiva, C., Balateu-Paños, D., Colom-Cadena, M., Gomez-Giro, G., Muñoz, L., Querol-Vilaseca, M., Pegueroles, J., et al. (2019) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra118.001290 · Cited by 219 · see citing works
Self-citationFortea, J., Carmona‐Iragui, M., Benejam, B., Fernández, S., Videla, L., Barroeta, I., Alcolea, D. A., Pegueroles, J., Muñoz, L., Belbin, O., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30285-0 · Cited by 203 · see citing works
Self-citationA prospective 14‐year longitudinal follow‐up of dementia in persons with D own syndrome
McCarron, M., McCallion, P., Reilly, E., & Mulryan, N. (2013) · Journal of Intellectual Disability Research · doi:10.1111/jir.12074 · Cited by 194 · see citing works
Agreement of amyloid PET and CSF biomarkers for Alzheimer's disease on Lumipulse
Alcolea, D., Pegueroles, J., Muñoz, L., Camacho, V., López‐Mora, D., Fernández‐León, A., Le Bastard, N., Huyck, E., Nadal, A., Olmedo, V., et al. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.50873 · Cited by 183 · see citing works
Self-citationAssociation of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years
Hithersay, R., Startin, C. M., Hamburg, S., Mok, K. Y., Hardy, J., Fisher, E. M. C., Tybulewicz, V. L. J., Nizetic, D., & Strydom, A. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.3616 · Cited by 176 · see citing works
Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease
Alcolea, D., Martínez-Lage, P., Sánchez-Juan, P., Olazarán, J., Antúnez, C., Izagirre, A., Ecay-Torres, M., Estanga, A., Clerigué, M., Guisasola, M. C., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001859 · Cited by 163 · see citing works
Self-citationPredictors of Age of Diagnosis and Survival of Alzheimer’s Disease in Down Syndrome
Sinai, A., Mokrysz, C., Bernal, J. D., Bohnen, I., Bonell, S., Courtenay, K., Dodd, K., Gazizova, D., Hassiotis, A., Hillier, R., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170624 · Cited by 137 · see citing works
Wiseman, F. K., Pulford, L. J., Barkus, C., Liao, F., Portelius, E., Webb, R., Chávez-Gutiérrez, L., Cleverley, K., Noy, S., Sheppard, O., et al. (2018) · Brain · doi:10.1093/brain/awy159 · Cited by 133 · see citing works
Galasko, D., Xiao, M., Xu, D., Smirnov, D., Salmon, D. P., Dewit, N., Vanbrabant, J., Jacobs, D., Vanderstichele, H., Vanmechelen, E., et al. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.11.002 · Cited by 133 · see citing works
Self-citationParvalbumin-immunoreactive neurons in the hippocampal formation of Alzheimer’s diseased brain
Brady, D. R., & Mufson, E. J. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00068-7 · Cited by 125 · see citing works
Alcolea, D. A., Clarimón, J., Carmona‐Iragui, M., Illán‐Gala, I., Morenas‐Rodríguez, E., Barroeta, I., Nogué, R. R., Sala, I., Sánchez‐Saudinós, M. B., Videla, L., et al. (2019) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.09.005 · Cited by 121 · see citing works
Self-citationNeuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia
van der Ende, E. L., Xiao, M., Xu, D., Poos, J. M., Panman, J. L., Jiskoot, L. C., Meeter, L. H., Dopper, E. G., Papma, J. M., Heller, C., et al. (2020) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-322493 · Cited by 94 · see citing works
Self-citationCerebral amyloid angiopathy in Down syndrome and sporadic and autosomal‐dominant Alzheimer's disease
Carmona‐Iragui, M., Balasa, M., Benejam, B., Alcolea, D. A., Fernández, S., Videla, L., Sala, I., Sánchez‐Saudinós, M. B., Morenas‐Rodríguez, E., Nogué, R. R., et al. (2017) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2017.03.007 · Cited by 88 · see citing works
Self-citationNeuroimaging and other modalities to assess Alzheimer's disease in Down syndrome
Neale, N., Padilla, C., Fonseca, L. M., Holland, T., & Zaman, S. H. (2017) · NeuroImage Clinical · doi:10.1016/j.nicl.2017.10.022 · Cited by 86 · see citing works
Castillo, S. E., Bueno, A. D., Ribas‐Vidal, N., Alsina, M. V., Alsina, R. N., & Alba, J. G. (2013) · Revista de Neurología · doi:10.33588/rn.5708.2013259 · Cited by 62 · see citing works
Alzheimer's disease and Down syndrome.
Schweber, M. S. (1989) · PubMed · Cited by 41 · see citing works
Sala, I., Illán‐Gala, I., Alcolea, D. A., Sánchez‐Saudinós, M. B., Salgado, S. A., Morenas‐Rodríguez, E., Subirana, A., Videla, L., Clarimón, J., Carmona‐Iragui, M., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170073 · Cited by 38 · see citing works
Self-citationCarmona‐Iragui, M., Santos, T., Videla, S., Fernández, S., Benejam, B., Videla, L., Alcolea, D. A., Blennow, K., Blesa, R., Lleó, A., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160827 · Cited by 26 · see citing works
Self-citationBejanin, A., Viard, A., Chételat, G., Clarys, D., Bernard, F., Pèlerin, A., Sayette, V. D. L., Eustache, F., & Desgranges, B. (2012) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2012.00107 · Cited by 10 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [23]Esteba-Castillo S Dalmau-Bueno A Ribas-Vidal N Vila-Alsina M Novell-Alsina R Garcia-Alba J Adaptation and validation of CAMDEX-DS (Cambridge examination for mental disorders of older people with Down’s syndrome and others with intellectual disabilities) in Spanish population with intellectual disabilities Rev Neurol 2013 57 337 346 24081888
Cited by
Sorted by citations
Alzheimer's disease associated with Down syndrome: a genetic form of dementia
Fortea, J., Zaman, S. H., Hartley, S., Rafii, M. S., Head, E., & Carmona-Iragui, M. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00245-3 · Cited by 357 · see citing works
Self-citationZhou, J., Wade, S. D., Graykowski, D., Xiao, M.-F., Zhao, B., Giannini, L. A. A., Hanson, J. E., van Swieten, J. C., Sheng, M., Worley, P. F., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adf0141 · Cited by 152 · see citing works
Self-citationGómez de San José, N., Massa, F., Halbgebauer, S., Oeckl, P., Steinacker, P., & Otto, M. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-021-02411-2 · Cited by 112 · see citing works
Zheng, Q., Song, B., Li, G., Cai, F., Wu, M., Zhao, Y., Jiang, L., Guo, T., Shen, M., Hou, H., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci152170 · Cited by 73 · see citing works
Boiten, W., van Steenoven, I., Xiao, M.-F., Worley, P., Noli, B., Cocco, C., Ferri, G.-L., Lemstra, A., & Teunissen, C. (2020) · Cells · doi:10.3390/cells10010038 · Cited by 42 · see citing works
Self-citationGlutamate receptor 4 as a fluid biomarker for the diagnosis of psychiatric disorders
Gómez de San José, N., Goossens, J., Al Shweiki, M. R., Halbgebauer, S., Oeckl, P., Steinacker, P., Danzer, K. M., Graf, H., Schönfeldt-Lecuona, C., Belbin, O., et al. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.10.010 · Cited by 9 · see citing works
Self-citation
- Authors
- Belbin, O., Xiao, M.-F., Xu, D., Carmona-Iragui, M., Pegueroles, J., Benejam, B., Videla, L., Fernández, S., Barroeta, I., Nuñez-Llaves, R., Montal, V., Vilaplana, E., Altuna, M., Clarimón, J., Alcolea, D., Blesa, R., Lleó, A., Worley, P. F., & Fortea, J.
- Affiliations
- Hospital de Sant Pau (ES)
- Johns Hopkins University (US)
- Corresponding author
- Belbin, Olivia
- ORCID
- Venue
- Molecular Neurodegeneration
- Published
- 2020-08-17
- Volume
- 15
- Issue
- 1
- Pages
- 46-46
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC7433053
- OpenAlex
- W3055276839
- Cited by
- 39
- References
- 40
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 8 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 1
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Instituto de Salud Carlos III (PI18/00327, PI17/01019, PI16/01825, PI17/01895, PI18/0335, CP18/00011)
- Centro de investigación biomedica en red sobre enfermedades neurodegenerativas (Program 1, Alzheimer Disease)
- National Institute on Aging (R35NS097966, R01AG056850-01A1, R21AG056974, R01AG061566)
- Departament de Salut, Generalitat de Catalunya (SLT006/17/125, SLT002/16/00099, SLT006/17/00119)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- NPTX2, Down syndrome, Alzheimer's disease, cerebrospinal fluid biomarkers, parvalbumin interneurons, GluA4, amyloid-beta 42, tau protein, cortical atrophy, glucose metabolism, prodromal Alzheimer's disease, Alzheimer's dementia, intellectual disability, early detection of Alzheimer's disease
- MeSH terms
- Pentraxins, Adult, Alzheimer Disease, C-Reactive Protein, Cross-Sectional Studies, Down Syndrome, Female, Humans, Male, Middle Aged, Nerve Tissue Proteins, Retrospective Studies, Biomarkers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
