Download PDF
CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2020; 78(02): 76-80
DOI: 10.1590/0004-282X20190151
Article

Complement factor H levels are decreased and correlated with serum C-reactive protein in late-onset Alzheimer's disease

Os níveis de fator H do complemento estão diminuídos e correlacionados com a proteína C-reativa sérica na doença de Alzheimer de início tardio
Guo LU 
1   Dezhou People's Hospital, Department of Neurology, Dezhou, Shandong, China.
,
Weihong LIU 
2   Dezhou People's Hospital, Department of Medicine Nuclear, Dezhou, Shandong, China.
,
Xinying HUANG 
1   Dezhou People's Hospital, Department of Neurology, Dezhou, Shandong, China.
,
Yanxin ZHAO 
3   Jinan Central Hospital, Jinan, Department of Neurology, Shandong, China.
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia. Despite numerous studies on the subject, the pathologies for AD are still unclear and there is still no ideal biomarker for diagnosis. The present study aimed to investigate clinical significance of human complement factor H (CFH) in patients with late-onset AD. Methods: The present prospective study included 187 late-onset AD patients who went to our hospital from January 2015 to December 2017. One hundred patients with mild cognitive impairment (MCI) and 80 healthy individuals who were age and gender matched to AD patients were enrolled as controls. Demographic data such as age, gender, and education duration were recorded. Blood samples were collected and serum levels of C-reactive protein (CRP), CFH, and brain-derived neurotrophic factor (BDNF) were determined by Enzyme-linked immunosorbent assay (ELISA). The mini-mental state examination (MMSE) score was measured for all patients. Results: No significant difference was found in age, gender, and education duration for all participants. The MMSE scores showed AD patients had lower MMES scores than the other two groups. All factors of CFH, CRP, and BDNF were dramatically decreased in AD patients compared with the MCI and the ealthy control. Levels of CFH were found to be positively correlated with levels of CRP; however, no significant correlation was found between CFH and BDNF, nor CFH and MMSE. Conclusion: CFH was decreased in late-onset AD patients, and serum levels of CFH was correlated with serum levels of CRP, but not MMSE and BDNF. These results may provide more clinical evidences for the role of CFH in AD patients.

Resumo

A doença de Alzheimer (DA) é a causa mais comum de demência. Apesar de inúmeros estudos sobre DA, suas patologias ainda não são claras e ainda não existe um biomarcador ideal para o diagnóstico da condição. O presente estudo teve como objetivo investigar a significância clínica do fator H do complemento humano (CFH) em pacientes com DA de início tardio. Métodos: O presente estudo prospectivo incluiu um total de 187 pacientes com DA de início tardio que foram ao nosso hospital entre janeiro de 2015 e dezembro de 2017. Cem pacientes com comprometimento cognitivo leve (CCL) e 80 indivíduos saudáveis com idade e sexo pareados com pacientes com DA foram incluídos como controle. Dados demográficos como idade, sexo e duração da educação foram registrados. As amostras de sangue foram coletadas e os níveis séricos de proteína C-reativa (PCR), CFH e fator neurotrófico derivado do cérebro (BDNF) foram determinados pelo ensaio imunoabsorvente ligado à enzima (ELISA). O escore do miniexame do estado mental (MEEM) foi medido para todos os pacientes. Resultados: Não foram encontradas diferenças significativas em idade, sexo e duração da educação para todos os participantes. Pacientes com DA tinham os menores escores de MEEM em relação aos outros dois grupos. Todos os fatores de CFH, PCR e BDNF diminuíram drasticamente em pacientes com DA em comparação com o CCL e o controle saudável. Os níveis de CFH mostraram correlação positiva com os níveis de PCR; no entanto, não foi encontrada correlação significativa entre CFH e BDNF, nem CFH e MEEM. Conclusão: A CFH diminuiu nos pacientes com DA de início tardio e os níveis séricos de CFH foram correlacionados com os níveis séricos de PCR, mas não o MEEM e o BDNF. Esses resultados podem fornecer mais evidências clínicas do papel da CFH em pacientes com DA.

Keywords:

complement factor H - late-onset Alzheimer's diseases - C-reactive protein

Palavras-chave:

fator H do complemento - doença de Alzheimer de início tardio - proteína C-reativa


Publication History

Received: 20 August 2019

Accepted: 16 September 2019

Article published online:
13 June 2023

© 2020. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016 Jun;8(6):595-608. https://doi.org/10.15252/emmm.201606210
  • 2 Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H, et al. Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol. 2016 Apr;15(5):455:532. https://doi.org/10.1016/S1474-4422(16)00062-4
  • 3 Heneka MT, Golenbock DT, Latz E. Innate immunity in Alzheimer's disease. Nat Immunol. 2015 Mar;16(3):229:36. https://doi.org/10.1038/ni.3102
  • 4 Kovács T. The olfactory system in Alzheimer’s disease: Pathology, pathophysiology and pathway for therapy. Transl Neurosci. 2013;4(1):34-45. https://doi.org/10.2478/s13380-013-0108-3
  • 5 Riley KP, Snowdon DA, Markesbery WR. Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study. Ann Neurol. 2010 May;51(5):567-77. https://doi.org/10.1002/ana.10161
  • 6 Olsson B, Lautner R, Andreasson U, Öhrfelt A, Portelius E, Bjerke M, et al. CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol. 2016 Jun;15(7):673-84. https://doi.org/10.1016/S1474-4422(16)00070-3
  • 7 Blennow K, Mattsson N, Schöll M, Hansson O, Zetterberg H. Amyloid biomarkers in Alzheimer's disease. Trends Pharmacol Sci. 2015 May;36(5):297-309. https://doi.org/10.1016/j.tips.2015.03.002
  • 8 Kamer AR, Craig RG, Pirraglia E, Dasanayake AP, Norman RG, Boylan RJ, et al. TNF-α and antibodies to periodontal bacteria discriminate between Alzheimer’s disease patients and normal subjects. J Neuroimmunol. 2009 Nov;216(1):92-7. https://doi.org/10.1016/j.tips.2015.03.002
  • 9 Ye X, Tai W, Zhang D. The early events of Alzheimer's disease pathology: from mitochondrial dysfunction to BDNF axonal transport deficits. Neurobiol Aging. 2012 Jun;33(6):1122.e1-.e10. https://doi.org/10.1016/j.neurobiolaging.2011.11.004
  • 10 Hooshmand B, Ahtiluoto S, Kareholt I, Solomon A, Winblad B, Soininen H, et al. Homocysteine, holotranscobalamin and risk of Alzheimer's disease: A longitudinal population-based study. Alzheimers Dement. 2009 Jul;5(4):P387-P. https://doi.org/10.1016/j.jalz.2009.04.1122
  • 11 Devčić S, Glamuzina L, Ruljancic N, Mihanovic M. There are no differences in IL-6, CRP and homocystein concentrations between women whose mothers had AD and women whose mothers did not have AD. Psychiatry Res. 2014 Dec;220(3):970-4. https://doi.org/10.1016/j.psychres.2014.08.059
  • 12 Laske C, Stellos K, Hoffmann N, Stransky E, Straten G, Eschweiler GH, et al. Higher BDNF serum levels predict slower cognitive decline in Alzheimer's disease patients. Int J Neuropsychoph. 2011 Apr;14(3):399-404. https://doi.org/10.1017/S1461145710001008
  • 13 Nilsson K, Gustafson L, Hultberg B. C-reactive protein level is decreased in patients with Alzheimer's disease and related to cognitive function and survival time. Clin Biochem. 2011 Oct;44(14-15):1205-8. https://doi.org/10.1016/j.clinbiochem.2011.07.011
  • 14 de la Fuente M, Blanco MJ, Pazos B, Fernández MI, Carracedo A, Sánchez-Salorio M, et al. Complement factor H. Ophthalmology. 2007 Jan;114(1):193.e1-.e2. https://doi.org/10.1016/j.ophtha.2006.10.004
  • 15 Rodríguez de Córdoba S, Esparza-Gordillo J, Jorge EGD, Lopez-Trascasa M, Sánchez-Corral P. The human complement factor H: functional roles, genetic variations and disease associations. Mol Immunol. 2004;41(4):355-67. https://doi.org/10.1016/j.molimm.2004.02.005
  • 16 Alexandrov PN, Pogue A, Bhattacharjee S, Lukiw WJ. Retinal amyloid peptides and complement factor H in transgenic models of Alzheimer's disease. Neuroreport. 2011 Aug;22(12):623-7. https://doi.org/10.1097/WNR.0b013e3283497334
  • 17 Williams, MA. Alzheimer's disease and age-related macular-degeneration: is complement factor H a common denominator? Belfast: Queens University; 2011.
  • 18 Williams MA, Haughton D, Stevenson M, Craig D, Passmore AP, Silvestri G. Plasma Complement factor H in Alzheimer's Disease. J Alzheimers Dis. 2015;45(2):369-72. https://doi.org/10.3233/JAD-142742
  • 19 Song IU, Chung SW, Kim YD, Maeng LS. Relationship between the hs-CRP as non-specific biomarker and Alzheimer's disease according to aging process. Int J Med Sci. 2015 Jun;12(8):613-7. https://doi.org/10.7150/ijms.12742
  • 20 Davis G, Baboolal N, Nayak S, McRae A. Sialic acid, homocysteine and CRP: Potential markers for dementia. Neurosci Letters. 2009 Nov;465(3):282-4. https://doi.org/10.1016/j.neulet.2009.09.035
  • 21 McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan E. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939-44. https://doi.org/10.1212/wnl.34.7.939
  • 22 Lukiw WJ, Alexandrov PN. Regulation of Complement Factor H (CFH) by Multiple miRNAs in Alzheimer’s Disease (AD) Brain. Mol Neurobiol. 2012 Aug;46(1):11-9. https://doi.org/10.1007/s12035-012-8234-4
  • 23 Li YY, Bhattacharjee S, Hill JM, Alexandrov PN, Pogue AI, Lukiw W. Chromosome 21-encoded miRNA-155 upregulation and complement factor H (CFH) deficits in Down syndrome (DS) and Alzheimer's disease (AD). Alzheimers Dement. 2012 Jul;8(4):P303-P. https://doi.org/10.1016/j.jalz.2012.05.826
  • 24 Wang Y, Hancock AM, Bradner J, Chung KA, Quinn JF, Peskind ER, et al. Complement 3 and Factor H in Human Cerebrospinal Fluid in Parkinson's Disease, Alzheimer's Disease, and Multiple-System Atrophy. Am J Pathol. 2011 Apr;178(4):1509-16. https://doi.org/10.1016/j.ajpath.2011.01.006
  • 25 Gezen-Ak D, Dursun E, Hanağası H, Bilgiç B, Lohman E, Araz ÖS, et al. BDNF, TNFα, HSP90, CFH, and IL-10 serum levels in patients with early or late onset Alzheimer's disease or mild cognitive impairment. J Alzheimers Dis. 2013 Aug;37(1):185-95. https://doi.org/10.3233/JAD-130497
  • 26 Yarchoan M, Louneva N, Xie SX, Swenson FJ, Hu W, Soares H, et al. Association of Plasma C-Reactive Protein Levels with Diagnosis of Alzheimer’s Disease. J Neurol Sci. 2013 Oct;333(1-2):9-12. https://doi.org/10.1016/j.jns.2013.05.028