C‐type lectin‐like receptor 2 and zonulin are associated with mild cognitive impairment and Alzheimer's disease
Abstract
OBJECTIVE: Increased permeability and changes in gut microbiota contributed to the pathogenesis of Alzheimer's disease (AD). Zonulin is a key modulator that regulates intestinal barrier function. Peripheral platelet alterations have been involved in AD pathology. C-type lectin-like receptor 2 (CLEC-2) is a receptor on the platelet surface for activation. The purpose of this study was to determine zonulin and CLEC-2 levels in mild cognitive impairment (MCI) and AD, and investigate the relationship between zonulin and CLEC-2. METHODS: In this study, CLEC-2 and zonulin levels were measured using ELISA assay in 110 AD patients, 110 MCI patients, and 110 non-demented control subjects. RESULTS: Increased CLEC-2 and zonulin levels were observed in MCI and AD patients. Furthermore, AD patients had higher CLEC-2 and zonulin levels compared with MCI patients. In addition, CLEC-2 levels were positively correlated with zonulin levels, after adjusting confounding factors (r = .592, P < .001). Multivariate analysis revealed that increased CLEC-2 and zonulin levels were significantly associated with reduced Mini-Mental State Examination (MMSE) score. CONCLUSIONS: C-type lectin-like receptor 2 is correlated with zonulin after adjusting confounding covariates. Moreover, increased CLEC-2 and zonulin are the significant factors for reduced MMSE score in MCI and AD. Further studies are needed.
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Gut microbiome alterations and intestinal barrier impairment have been observed in patients with MCI, AD, PD, and ALS.
“Gut microbiome alterations and intestinal barrier impairment have been observed in patients with MCI, AD, PD, and ALS patients.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [626]
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
McKhann, 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
Winblad, B., Palmer, K., Kivipelto, M., Jelic, V., Fratiglioni, L., Wahlund, L. ‐., Nordberg, A., Bäckman, L., Albert, M., Almkvist, O., et al. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01380.x · Cited by 4,946 · see citing works
Mitchell, A. J., & Shiri‐Feshki, M. (2009) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2008.01326.x · Cited by 1,659 · see citing works
Fasano, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00003.2008 · Cited by 979 · see citing works
Brain-Gut-Microbiota Axis in Alzheimer’s Disease
Kowalski, K., & Mulak, A. (2019) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm18087 · Cited by 826 · see citing works
Intestinal permeability and its regulation by zonulin: Diagnostic and therapeutic implications
Fasano, A. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.08.012 · Cited by 402 · see citing works
Asmar, R. E., Panigrahi, P., Bamford, P. D., Berti, I., Not, T., Coppa, G. V., Catassi, C., & Fasano, A. (2002) · Gastroenterology · doi:10.1053/gast.2002.36578 · Cited by 365 · see citing works
Zonulin, regulation of tight junctions, and autoimmune diseases
Fasano, A. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06538.x · Cited by 365 · see citing works
Hawkes, C. A., Härtig, W., Kacza, J., Schliebs, R., Weller, R. O., Nicoll, J. A. R., & Carare, R. O. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0801-7 · Cited by 359 · see citing works
Carare, R. O., Hawkes, C. A., Jeffrey, M., Kalaria, R. N., & Weller, R. O. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12042 · Cited by 207 · see citing works
The role of gut microbiota in pathogenesis of Alzheimer's disease
Bostancıklıoğlu, M. (2019) · Journal of Applied Microbiology · doi:10.1111/jam.14264 · Cited by 200 · see citing works
Bermejo, P., Martín-Aragón, S., Benedí, J., Susín, C., Felici, E., Gil, P., Ribera, J. M., & Villar, Á. M. (2008) · Immunology Letters · doi:10.1016/j.imlet.2008.02.002 · Cited by 178 · see citing works
Zhu, W., Buffa, J. A., Wang, Z., Warrier, M., Schugar, R., Shih, D. M., Gupta, N., Gregory, J. C., Org, E., Fu, X., et al. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14234 · Cited by 161 · see citing works
Jäckel, S., Kiouptsi, K., Lillich, M., Hendrikx, T., Khandagale, A., Kollar, B., Hörmann, N., Reiss, C., Subramaniam, S., Wilms, E., et al. (2017) · Blood · doi:10.1182/blood-2016-11-754416 · Cited by 156 · see citing works
Secretion of Alzheimer's disease Abeta amyloid peptide by activated human platelets.
Li, Q., Whyte, S., Tanner, J. E., Evin, G. M., Beyreuther, K. T., & Masters, C. L. (1998) · PubMed · Cited by 155 · see citing works
Schellekens, D. H. S. M., Grootjans, J., Dello, S. A. W. G., van Bijnen, A. A. J. H. M., van Dam, R. M., Dejong, C. H. C., Derikx, J. P. M., & Buurman, W. A. (2013) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e3182a87e3e · Cited by 142 · see citing works
Li, Q., Berndt, M., Bush, A. I., et al. (1994) · Blood · doi:10.1182/blood.v84.1.133.133 · Cited by 129 · see citing works
Stellos, K., Panagiota, V., Kogel, A. J. B. D., Leyhe, T., Gawaz, M., & Laske, C. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.140 · Cited by 118 · see citing works
Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer’s disease
Forlenza, O. V., Torres, C. A., Talib, L. L., et al. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.06.002 · Cited by 110 · see citing works
Blood cell markers in Alzheimer Disease: Amyloid Precursor Protein form ratio in platelets
Borroni, B., Agosti, C., Marcello, E. E., Luca, M. D., & Padovani, A. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.08.004 · Cited by 88 · see citing works
Platelet β-secretase activity is increased in Alzheimer's disease
Johnston, J. A., Liu, W. W., Coulson, D. T. R., Todd, S., Murphy, S., Brennan, S., Foy, C. J., Craig, D., Irvine, G. B., & Passmore, A. P. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.11.003 · Cited by 76 · see citing works
Wang, R., Jin, D., Li, Y., & Liang, Q.-C. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.01.014 · Cited by 63 · see citing works
Self-citationCoated-platelet levels and progression from mild cognitive impairment to Alzheimer disease
Prodan, C. I., Ross, E. D., Stoner, J. A., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e3182074bd2 · Cited by 62 · see citing works
Mean platelet volume and platelet distribution width in vascular dementia and Alzheimer’s disease
Liang, Q.-C., Jin, D., Li, Y., et al. (2013) · Platelets · doi:10.3109/09537104.2013.831064 · Cited by 60 · see citing works
Crosstalk between Gut Microbiota and Central Nervous System: A Focus on Alzheimer's Disease
Junges, V. M., Closs, V. E., Nogueira, G., & Gottlieb, M. G. V. (2018) · Current Alzheimer Research · doi:10.2174/1567205015666180904155908 · Cited by 58 · see citing works
Platelet CLEC-2: Roles Beyond Hemostasis
Tsukiji, N., Shirai, T., Osada, M., Inoue, O., Ozaki, Y., & Suzuki‐Inoue, K. (2017) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0037-1604090 · Cited by 56 · see citing works
Reduced phospholipid breakdown in Alzheimer’s brains: a 31P spectroscopy study
Forlenza, O. V., Wacker, P., Nunes, P. V., Yacubian, J., de Castro, C. C., Otaduy, M. C. G., & Gattaz, W. F. (2005) · Psychopharmacology · doi:10.1007/s00213-005-2168-8 · Cited by 54 · see citing works
Queiroz, D. M. M., Rocha, A. M. C., Rocha, G. A., Cinque, S., de Oliveira, A. G., Godoy, A., & Tanno, H. (2006) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-3150-y · Cited by 51 · see citing works
Iarlori, C., Gambi, D., Gambi, F., Lucci, I., Feliciani, C., Salvatore, M., & Reale, M. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.04.007 · Cited by 44 · see citing works
AβPeptide Originated from Platelets Promises New Strategy in Anti-Alzheimer’s Drug Development
Inyushin, M. Y., Sanabria, P., Rojas, L. V., Kucheryavykh, Y. V., & Kucheryavykh, L. Y. (2017) · BioMed Research International · doi:10.1155/2017/3948360 · Cited by 30 · see citing works
Platelets: Peripheral Biomarkers of Dementia?
Akingbade, O. E. S., Gibson, C. L., Kalaria, R. N., & Mukaetova-Ladinska, E. B. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180181 · Cited by 30 · see citing works
Mukaetova‐Ladinska, E. B., Abdel‐All, Z., Dodds, S., Andrade, J., da Silva, J. A., Kalaria, R. N., & O'Brien, J. T. (2012) · Age and Ageing · doi:10.1093/ageing/afr171 · Cited by 26 · see citing works
Krzystanek, E., Krzystanek, M., Opala, G., Trzeciak, H. I., Siuda, J. S., & Małecki, A. (2007) · Journal of Neural Transmission · doi:10.1007/s00702-007-0669-9 · Cited by 25 · see citing works
Yoon, H., Kim, H., Lee, S. H., Kim, S. J., Chang, Y., Ryu, S., Shin, H., Kim, H., & Lee, J. H. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8020230 · Cited by 15 · see citing works
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
Zhao, Z., Ning, J., Bao, X.-Q., Shang, M., Ma, J., Li, G., & Zhang, D. (2021) · Microbiome · doi:10.1186/s40168-021-01107-9 · Cited by 616 · see citing works
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Pellegrini, C., Fornai, M., D'Antongiovanni, V., Antonioli, L., Bernardini, N., & Derkinderen, P. (2023) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(22)00241-2 · Cited by 239 · see citing works
Wasiak, J., & Gawlik-Kotelnicka, O. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114459 · Cited by 47 · see citing works
- Authors
- Wang, X., Liu, G., Gao, Q., Li, N., & Wang, R.
- Affiliations
- Harbin Medical University (CN)
- Department of Rehabilitation Medicine General Hospital of Heilongjiang General Administration of Agriculture and Reclamation Harbin Heilongjiang China
- Department of Internal Medicine Harbin Medical University Cancer Hospital Harbin Medical University Harbin Heilongjiang China
- Venue
- Acta Neurologica Scandinavica
- Publisher
- Wiley
- Published
- 2019-11-25
- Volume
- 141
- Issue
- 3
- Pages
- 250-255
- ISSN
- 0001-6314 (ISSN-L)
- 1600-0404
- OpenAlex
- W2982993456
- Cited by
- 51
- References
- 35
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 11 · 2023: 10 · 2022: 9 · 2021: 8 · 2020: 4
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Acta Neurologica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- CLEC-2, zonulin, Alzheimer's disease, mild cognitive impairment, platelets, intestinal permeability, gut microbiota, intestinal barrier function, cognitive impairment, biomarkers
- MeSH terms
- Aged, Alzheimer Disease, Female, Haptoglobins, Humans, Male, Middle Aged, Protein Precursors, Biomarkers, Lectins, C-Type, Cognitive Dysfunction
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