Abstract
It is known that stress and immune systems are related with Alzheimer’s disease (AD). However, the relationship of both systems in the progression of disease is not clearly demonstrated. Hair cortisol and salivary immunoglobulin A (IgA) were quantified in 49 patients with mild, moderate, and severe AD. A significant change was seen in both molecules as AD progressed from mild to moderate and severe. Low levels of cortisol were observed in mild AD patients compared with moderate and severe. However, IgA showed a contrary pattern. High levels were observed in mild AD patientes but low in moderate and severe AD subjects. The secretion of cortisol and IgA seems to be very different at the start compared with posterior development of AD suggesting that neuroinflammation can be involved. Both molecules could be used as possible therapeutical tools.
Abbreviations
- AD:
-
Alzheimer’s disease
- AFAV:
-
Asociacion Familiares Alzheimer Valencia
- CSF:
-
Cerebrospinal fluid
- ELISA:
-
Enzyme-linked immunosorbent
- IgA:
-
Immunoglobulin A
- MMSE:
-
Mini Mental State Examination
References
Ashraf GM, Azhar A, Zia Q et al (2018) Relationship between CNS and immunology: correlation with psychology. Curr Drug Metab 19:847–855. https://doi.org/10.2174/1389200219666180129142534
Bisht K, Sharma K, Tremblay MÈ (2018) Chronic stress as a risk factor for Alzheimer’s disease: roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress. Neurobiol Stress 9:9–21. https://doi.org/10.1016/j.ynstr.2018.05.003
Cuadrado-Tejedor M, Ricobaraza A, Frechilla D et al (2012) Chronic mild stress accelerates the onset and progression of the Alzheimer’s disease phenotype in Tg2576 mice. J Alzheimers Dis 28:567–578. https://doi.org/10.3233/jad-2011-110572
De la Rubia Ortí JE, Sancho Castillo S, Benlloch M et al (2017) Impact of the relationship of stress and the immune system in the appearance of Alzheimer’s disease. J Alzheimers Dis 55:899–903. https://doi.org/10.3233/jad-160903
Doss S, Wandinger KP, Hyman BT et al (2014) High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types. Ann Clin Transl Neurol 1:822–832. https://doi.org/10.1002/acn3.120
Elovaara I, Palo J, Erkinjuntti T et al (1985) Serum and cerebrospinal fluid proteins and the blood–brain barrier in Alzheimer’s disease and multi-infarct dementia. Eur Neurol 26:229–234. https://doi.org/10.1159/000116341
Feller S, Vigl M, Bergmann MM et al (2014) Predictors of hair cortisol concentrations in older adults. Psychoneuroendocrinoly 39:132–140. https://doi.org/10.1016/j.psyneuen.2013.10.007
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Psychiatry Res 12:189–198
Franceschi C, Bonafè M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann NY Acad Sci 908:244–254
Francis JL, Gleeson M, Pyne DB et al (2005) Variation of salivary immunoglobulins in exercising and sedentary populations. Med Sci Sports Exerc 37:571–578
Furtado M, Katzman MA (2015) Examining the role of neuroinflammation in major depression. Psychiatry Res 229:27–36. https://doi.org/10.1016/j.psychres.2015.06.009
Goldeck D, Witkowski JM, Fülop T et al (2016) Peripheral immune signatures in Alzheimer disease. Curr Alzheimer Res 13:739–749
Gómez-Gallego M, Gómez-García J (2018) Stress and verbal memory in patients with Alzheimer’s disease: different role of cortisol and anxiety. Aging Ment Health 24:1–7. https://doi.org/10.1080/13607863.2018.1506741
Guedes JR, Lao T, Cardoso AL et al (2018) Roles of microglial and monocyte chemokines and their receptors in regulating Alzheimer’s disease-associated amyloid-β and Tau pathologies. Front Neurol 9:549. https://doi.org/10.3389/fneur.2018.00549
Guerreiro R, Wojtas A, Bras J et al (2013) TREM2 variants in Alzheimer’s disease. N Engl J Med 368:117–127. https://doi.org/10.1056/nejmoa1211851
Herrero MT, Estrada C, Maatouk L et al (2015) Inflammation in Parkinson’s disease: role of glucocorticoids. Front Neuroanat 9:32. https://doi.org/10.3389/fnana.2015.00032
Huang CW, Lui CC, Chang WN et al (2009) Elevated basal cortisol level predicts lower hippocampal volume and cognitive decline in Alzheimer’s disease. J Clin Neurosci 16:1283–1286. https://doi.org/10.1016/j.jocn.2008.12.026
Jay TR, Hirsch AM, Broihier ML et al (2017) Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer’s disease. J Neurosci 37:637–647. https://doi.org/10.1523/jneurosci.2110-16.2016
Jonsson T, Stefansson H, Steinberg S et al (2013) Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med 368:107–116. https://doi.org/10.1056/nejmoa1211103
Justice NJ (2018) The relationship between stress and Alzheimer’s disease. Neurobiol Stress 8:127–133. https://doi.org/10.1016/j.ynstr.2018.04.002
Katsumoto A, Takeuchi H, Takahashi K et al (2018) Microglia in Alzheimer’s disease: risk factors and inflammation. Front Neurol 9:978. https://doi.org/10.3389/fneur.2018.00978
Leblhuber F, Walli J, Tilz GP et al (1998) Systemic changes of the immune system in patients with Alzheimer’s dementia. Dtsch Med Wochensch 123:787–791. https://doi.org/10.1055/s-2007-1024069
Monteiro RC (2010) Role of IgA and IgA fc receptors in inflammation. J Clin Immunol 30:1–9. https://doi.org/10.1007/s10875-009-9338-0
Notarianni E (2013) Hypercortisolemia and glucocorticoid receptor-signaling insufficiency in Alzheimer’s disease initiation and development. Curr Alzheimer Res 10:714–731
Ricci S, Fuso A, Ippoliti F et al (2012) Stress-induced cytokines and neuronal dysfunction in Alzheimer’s disease. J Alzheimers Dis 28:11–24. https://doi.org/10.3233/jad-2011-110821
Rodríguez-Arias M, García-Pardo MP, Montagud-Romero S et al (2013) The role of stress in psychostimulant addiction: treatment approaches based on animal models. New York, p 153–220
Song WM, Colonna M (2018) The microglial response to neurodegenerative disease. Adv Immunol 139:1–50. https://doi.org/10.1016/bs.ai.2018.04.002
Tan ZS, Beiser AS, Vasan RS et al (2007) Inflammatory markers and the risk of Alzheimer disease The Framingham Study. Neurology 68:1902–1908. https://doi.org/10.1212/01.wnl.0000263217.36439.da
Tecles F, Fuentes-Rubio M, Tvarijonaviciute A et al (2014) Assessment of stress associated with an oral public speech in veterinary students by salivary biomarkers. J Vet Med Educ 41:37–43. https://doi.org/10.3138/jvme.0513-073r1
Tortosa-Martínez J, Manchado C, Cortell-Tormo JM et al (2018) Exercise, the diurnal cycle of cortisol and cognitive impairment in older adults. Neurobiol Stress 9:40–47. https://doi.org/10.1016/j.ynstr.2018.08.004
Acknowledgements
The researchers of this study are grateful to all participants for their collaboration in the project. A special thank you to AFAV Association for providing the places and professionals to collect the data.
Consent for Publication
This manuscript has been read and approved by all authors, has not been previously published, and is not under simultaneous consideration by another journal. The authors give consent for publication in Molecular Neurodegeneration.
Availability of Data and Materials
Materials and/or datasets used/generated are included in the manuscript or available upon reasonable request.
Declarations
The authors declare that this work is original and has not been published elsewhere nor is it currently under consideration for publication elsewhere.
Funding
This study was supported with funding from the company Alquería Ortí C.B and partially by Grant PROMETEO 94/2016 of the Generalitat Valenciana.
Author information
Authors and Affiliations
Contributions
JERO and MPGP conceived and designed the experiments and were responsible for the interpretation of the results; Mariano JR performed, analyzed the data, and made the figure of the results; SSC performed the ELISA technique. VPG and FJR wrote the first draft of the paper and JERO and MPGP wrote the final version of the manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
The authors of this manuscript declare that they have no competing interests.
Ethics Approval
The study was approved by the Ethics Committee of the Universidad de Valencia and all participants signed informed consent.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Annexed 1: Declaración de Consentimiento Informado
Annexed 1: Declaración de Consentimiento Informado
--------, a------ de-------- de 2017
D. /Dña ………………………, de …. años de edad y con DNI nº ……….., manifiesta que ha sido informado/a de que el proyecto sigue la normativa de la Declaración de Helsinki de 1964 y de sus posteriores actualizaciones (la más reciente hecha en Brasil, octubre de 2013), así mismo ha sido informado sobre los beneficios psicológicos y de salud fisica que podría suponer la participación en el Proyecto “Estudio longitudinal del estado neurofisiológico y cognitivo en pacientes institucionalizados con demencia tipo Alzheimer. Aplicación de terapias no farmacológicas en la mejora de la enfermedad” para las áreas personal, social y familiar del paciente y para la investigación en psicología. Así mismo manifiesta que ha sido informado/a del tipo de pruebas y procedimientos que se le aplicarán a su familiar y de los objetivos del proyecto, y de que se participa sin ánimo de lucro.
Manifiesta que también ha sido informado/a que sus datos personales y los de su familiar serán protegidos e incluidos en un fichero que deberá estar sometido a y con las garantías de la ley 15/1999 de 13 de diciembre.
Tomando ello en consideración, OTORGO mi CONSENTIMIENTO a participar en esta investigación.
Fecha:
Firma del participante (o representante legal):
Firma de los investigadores:
Rights and permissions
About this article
Cite this article
de la Rubia Ortí, J., Prado-Gascó, V., Sancho Castillo, S. et al. Cortisol and IgA are Involved in the Progression of Alzheimer’s Disease. A Pilot Study. Cell Mol Neurobiol 39, 1061–1065 (2019). https://doi.org/10.1007/s10571-019-00699-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-019-00699-z