Alzheimer’s disease, biomarkers and the role of the inflammatory profile in the cerebrospinal fluid

Doença de Alzheimer, biomarcadores e o papel do perfil inflamatório no líquido cefalorraquidiano

Autores

Palavras-chave:

Alzheimer's disease, P-tau, Neuroinflammation, Lactate, LDH

Resumo

Introduction: Amyloid plaques and neurofibrillary tangles are associated with neuronal injury in Alzheimer's disease (AD). Objective: To investigate the relationship between biomarkers of neurodegeneration and the inflammatory profile in the cerebrospinal fluid (CSF) of patients with AD and mild cognitive impairment (MCI). Methods: A cross-sectional study including data on biochemical markers and clinical characteristics related to CSF biomarkers (p-tau, t-tau, and Aβ1-42) of 51 patients with MCI or AD was performed. Results:  A positive correlation between lactate dehydrogenase (LDH) and both p-tau (r=0.548; p<0.001) and t-tau (r=0.757; p<0.001), a negative correlation between lactate and p-tau (r=0.399; p<0.005), and a positive correlation between aspartate aminotransferase and p-tau (r=0.489; p<0.001) were found. Discussion: The positive correlation between LDH and tau protein points to a role for oxidative stress in AD. The negative correlation between lactate and p-tau suggests a detrimental effect of tau protein on cell metabolism. Conclusions: Inflammatory biomarkers might aid in AD workup. Technical simplicity and their potential association with tau protein warrant further research into LDH and lactate in AD.

Downloads

Não há dados estatísticos.

Referências

AISEN, Paul S. et al. On the path to 2025: Understanding the Alzheimer’s disease continuum. Alzheimer’s Research and Therapy, [S. l.], v. 9, n. 1, p. 1–10, 2017. DOI: 10.1186/s13195-017-0283-5.

ALEXOPOULOS, Panagiotis et al. Conflicting cerebrospinal fluid biomarkers and progression to dementia due to Alzheimer’s disease. Alzheimer’s Research and Therapy, [S. l.], v. 8, n. 1, p. 51, 2016. DOI: 10.1186/s13195-016-0220-z.

ASSOCIATION ALZHEIMER, Alzheimer. 2016 Alzheimer ’ s disease facts and figures. Alzheimer’s & Dementia, [S. l.], v. 12, n. 4, p. 459–509, 2016. DOI: 10.1016/j.jalz.2016.03.001.

BAYART, Jean Louis; HANSEEUW, Bernard; IVANOIU, Adrian; VAN PESCH, Vincent. Analytical and clinical performances of the automated Lumipulse cerebrospinal fluid Aβ42 and T-Tau assays for Alzheimer’s disease diagnosis. Journal of Neurology, [S. l.], v. 266, n. 9, p. 2304–2311, 2019. DOI: 10.1007/s00415-019-09418-6.

BLOUDEK, Lisa M.; SPACKMAN, D. Eldon; BLANKENBURG, Michael; SULLIVAN, Sean D.; PHARMA, Healthcare. Review and Meta-Analysis of Biomarkers and Diagnostic Imaging in Alzheimer ’ s Disease. [S. l.], v. 26, p. 627–645, 2014. DOI: 10.3233/JAD-2011-110458.

DOECKE, James D. et al. Concordance Between Cerebrospinal Fluid Biomarkers with Alzheimer’s Disease Pathology Between Three Independent Assay Platforms. Journal of Alzheimer’s disease : JAD, [S. l.], v. 61, n. 1, p. 169–183, 2018. DOI: 10.3233/JAD-170128.

FERREIRA, Daniel; PERESTELO-PÉREZ, Lilisbeth; WESTMAN, Eric; WAHLUND, Lars-olof; SARRÍA, Antonio; SERRANO-AGUILAR, Pedro. Meta-review of CSF core biomarkers in Alzheimer ’ s disease : the state-of-the-art after the new revised diagnostic criteria. [S. l.], v. 6, n. March, p. 1–24, 2014. DOI: 10.3389/fnagi.2014.00047.

FRÖLICH, Lutz et al. Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer’s dementia. Alzheimer’s research & therapy, [S. l.], v. 9, n. 1, p. 84, 2017. DOI: 10.1186/s13195-017-0301-7.

GRASSET, Leslie; BRAYNE, Carol; JOLY, Pierre; JACQMIN-GADDA, Hélène; PERES, Karine; FOUBERT-SAMIER, Alexandra; DARTIGUES, Jean François; HELMER, Catherine. Trends in dementia incidence: Evolution over a 10-year period in France. Alzheimer’s and Dementia, [S. l.], v. 12, n. 3, p. 272–280, 2016. DOI: 10.1016/j.jalz.2015.11.001.

HUMPEL, Christian. Identifying and validating biomarkers for Alzheimer’s disease. Trends in Biotechnology, [S. l.], v. 29, n. 1, p. 26–32, 2011. DOI: 10.1016/j.tibtech.2010.09.007.

JACK, Clifford R.; ALBERT, Marilyn S.; KNOPMAN, David S.; MCKHANN, Guy M.; SPERLING, Reisa A.; CARRILLO, Maria C.; THIES, Bill; PHELPS, Creighton H. Introduction to the recommendations from the National Institute on Aging-Alzheimer ’ s Association workgroups on diagnostic guidelines for Alzheimer ’ s disease. Alzheimer’s & Dementia, [S. l.], v. 7, n. 3, p. 257–262, 2011. DOI: 10.1016/j.jalz.2011.03.004.

KOYCHEV, Ivan et al. PET Tau and Amyloid-β Burden in Mild Alzheimer’s Disease: Divergent Relationship with Age, Cognition, and Cerebrospinal Fluid Biomarkers. Journal of Alzheimer’s disease : JAD, [S. l.], v. 60, n. 1, p. 283–293, 2017. DOI: 10.3233/JAD-170129.

LEMOS, Glesley Vito Lima; RIBEIRO, Leidson Rodrigo Teixeira; HABIB, Thiago Fraga; FERRAZ, Conceição Neves; DE MELO, Paulo Roberto Santana; GIUFFRIDA, Fernando de Mello Almada; JÚNIOR, Aníbal de Freitas Santos; CERQUEIRA, Bruno Veloso. An interrelationship between neuroinflammation and progression of Alzheimer’s disease (AD) / A inter-relação entre a neuroinflamação e a progressão da Doença de Alzheimer (DA). Brazilian Journal of Development, [S. l.], v. 7, n. 4, p. 41689–41701, 2021. DOI: 10.34117/bjdv7n4-570.

LIGUORI, C.; STEFANI, A.; SANCESARIO, G.; SANCESARIO, G. M.; MARCIANI, M. G.; PIERANTOZZI, M. CSF lactate levels, τ proteins, cognitive decline: a dynamic relationship in Alzheimer’s disease. Journal of Neurology, Neurosurgery & Psychiatry, [S. l.], v. 86, n. 6, p. 655–659, 2015. b. DOI: 10.1136/jnnp-2014-308577.

LU, Weitian; HUANG, Juan; SUN, Shanquan; HUANG, Siqin; GAN, Shengwei; XU, Jin; YANG, Mei; XU, Shiye; JIANG, Xuli. Changes in lactate content and monocarboxylate transporter 2 expression in Aβ25-35-treated rat model of Alzheimer’s disease. Neurological Sciences, [S. l.], v. 36, n. 6, p. 871–876, 2015. DOI: 10.1007/s10072-015-2087-3.

MCKHANN, Guy M. et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s and Dementia, [S. l.], v. 7, n. 3, p. 263–269, 2011. DOI: 10.1016/j.jalz.2011.03.005.

NHO, Kwangsik et al. Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers. JAMA network open, [S. l.], v. 2, n. 7, p. e197978, 2019. DOI: 10.1001/jamanetworkopen.2019.7978.

PORTELIUS, Erik; BRINKMALM, Gunnar; PANNEE, Josef; ZETTERBERG, Henrik; BLENNOW, Kaj; DAHLÉN, Rahil; BRINKMALM, Ann; GOBOM, Johan. Proteomic studies of cerebrospinal fluid biomarkers of Alzheimer’s disease: An update. Expert Review of Proteomics, [S. l.], v. 14, n. 11, p. 1007–1020, 2017. DOI: 10.1080/14789450.2017.1384697.

RIVERO-SANTANA, Amado; FERREIRA, Daniel; PERESTELO-PÉREZ, Lilisbeth; WESTMAN, Eric; WAHLUND, Lars-Olof; SARRÍA, Antonio; SERRANO-AGUILAR, Pedro. Cerebrospinal Fluid Biomarkers for the Differential Diagnosis between Alzheimer’s Disease and Frontotemporal Lobar Degeneration: Systematic Review, HSROC Analysis, and Confounding Factors. Journal of Alzheimer’s disease : JAD, [S. l.], v. 55, n. 2, p. 625–644, 2017. DOI: 10.3233/JAD-160366.

SCARABINO, Daniela; BROGGIO, Elisabetta; GAMBINA, Giuseppe; CORBO, Rosa Maria. Leukocyte telomere length in mild cognitive impairment and Alzheimer’s disease patients. Experimental Gerontology, [S. l.], v. 98, p. 143–147, 2017. DOI: 10.1016/j.exger.2017.08.025.

VAN WAALWIJK VAN DOORN, Linda J. C. et al. Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer’s Disease Patients and Controls after Correction for Ventricular Volumes. Journal of Alzheimer’s Disease, [S. l.], v. 56, n. 2, p. 543–555, 2017. DOI: 10.3233/JAD-160668.

VILATELA, Alonso; MARISOL, L.; YESCAS-G, Petra. Genetics of Alzheimer’ s Disease. [S. l.], v. 43, p. 622–631, 2012. DOI: 10.1016/j.arcmed.2012.10.017.

WYSS-CORAY, Tony; ROGERS, Joseph. Inflammation in Alzheimer disease-A brief review of the basic science and clinical literature. Cold Spring Harbor Perspectives in Medicine, [S. l.], v. 2, n. 1, p. 1–24, 2012. DOI: 10.1101/cshperspect.a006346.

YAO, Kai; ZHAO, Yong Fei; ZU, Heng Bing. Melatonin receptor stimulation by agomelatine prevents Aβ-induced tau phosphorylation and oxidative damage in PC12 cells. Drug Design, Development and Therapy, [S. l.], v. 13, p. 387–396, 2019. DOI: 10.2147/DDDT.S182684.

YIN, Fei; SANCHETI, Harsh; PATIL, Ishan; CADENAS, Enrique. Energy metabolism and inflammation in brain aging and Alzheimer’s disease. Free Radical Biology and Medicine, [S. l.], v. 100, p. 108–122, 2016. DOI: 10.1016/j.freeradbiomed.2016.04.200.

ZHANG, Mao; CHENG, Xiaofang; DANG, Ruozhi; ZHANG, Weiwei; ZHANG, Jie; YAO, Zhongxiang. Lactate deficit in an Alzheimer disease mouse model: The relationship with neuronal damage. Journal of Neuropathology and Experimental Neurology, [S. l.], v. 77, n. 12, p. 1163–1176, 2018. DOI: 10.1093/jnen/nly102.

Downloads

Publicado

2024-04-03

Edição

Seção

Articles