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ISSN 1527-3172 (Electronic)

2017, Number 2-3

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MEDICC Review 2017; 19 (2-3)

Association of antineuronal antibody levels with cognitive impairment in older cuban adults

Cristiá-Lara L, Sosa-Pérez S, Urrutia-Amble N, Garrudo-Guirado A, Posada-García A, Galán-García L, Verde-Corvo L, Rodríguez-Morera M, Dorestes-Brown M, Bobes-León MA, Rodríguez-Tanty C, Sablón-Carrazana M, Manrique-Suárez V

Language: English
References: 60
Page: 32-39
PDF size: 236.24 Kb.


ABSTRACT

Introduction Alzheimer disease is the main cause of dementia associated with aging in Cuba and the world. Development of methods for early diagnosis is vital to increasing intervention effectiveness and improving patient quality of life. Recent studies have shown associations between alterations in serum levels of antineuronal antibodies and Alzheimer disease pathology. However, the specific relationship between such antineuronal antibodies and Alzheimer pathogenesis remains unclear because of the great variety of antibodies identified and their heterogeneity among patients and nondemented controls.
Objective Assess the association between serum levels of antibodies against neuronal antigens (total brain protein, aldolase and amyloid beta protein) and cognitive performance in older Cuban adults.
Methods A cross-sectional pilot study was conducted of adults aged ≥ 65 years living in Havana’s Playa Municipality and Artemisa Province (southwest of Havana). A sociodemographic and risk factor questionnaire was administered, neuropsychological assessment conducted, and physical and neurological examinations performed. A relative or caregiver was also interviewed. Laboratory tests included: complete blood count, glycemia, lipid panel, and apolipoprotein E genotype. Of 143 individuals studied, 33 were cognitively normal, 52 had mild cognitive impairment, and 58, probable Alzheimer disease. Serum antibody levels were determined by ELISA and compared using covariance analysis with a significance level of 0.05. ELISA specificity, sensitivity and predictive value were assessed by analyzing their respective diagnostic performance curves.
Results Patients with probable Alzheimer disease performed least well on the mini mental state examination (cognitively normal 28.8, SD 1.2; mild cognitive impairment 27.4, SD 2.2; probable Alzheimer disease 12.9, SD 6.5; ANOVA p < 0.001). The percentage of Apo E4 carriers was seven times greater in the group with probable Alzheimer disease than in the cognitively normal group. Among the antibodies studied, only those against amyloid beta peptide had levels significantly higher in the Alzheimer disease group than in the cognitively normal group (p = 0.007) and the group with mild cognitive impairment (p = 0.002).
Conclusions Results support the presence of an autoimmune component in Alzheimer disease and suggest that serum anti–amyloid-beta could be used for its diagnosis.


REFERENCES

  1. Prince M, Wimo A, Guerchet M, Ali GC, Wu YT. World Alzheimer Report 2015—The Global Impact of Dementia: An analysis of p revalence, incidence, cost and trends. London: Alzheimer’s Disease International; 2015. 83 p.

  2. United Nations Population Division. World Population Ageing, 2015 [Internet]. New York: United Nations; 2015 [cite d 2016 Apr 22]. 4 p. Available from: https://www.un.org/en/development/ desa/population/publications/pdf/ageing/Popula tionAgeingAndDevelopment2015.pdf

  3. Duque-Castaño A, Roldán MI, Arango-Viana JC, Arcos-Burgos M, Cubillo H, Lopera F. [Neuropathological fi ndings in e arly-onset Alzheimer’s disease (E280a-PS1 mutation)]. Rev Neurol. 1999 Jul 1–15;29(1):1–6. Spanish.

  4. Bertram L, Lill CM, Tanzi RE. The genetics of Alzheimer disease: back to the future. Neuron. 2010 Oct 21;68(2):270–8 1.

  5. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDSADRDA 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.

  6. American Psychiatric Association. Diagnostic and statistical manual of mental disorder. 4th ed. Virginia: American P sychiatric Association; 1994 Jan 15. 886 p.

  7. Folstein MF, Folstein SE, McHugh PR. “Minimental state”. A practical method for grading the cognitive state of pati ents for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–98.

  8. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993 Nov;43(11):2412–4.

  9. Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Ins titute on Aging Alzheimer Disease Centers, 2005–2010. J Neuropathol Exp Neurol. 2012 Apr;71(4):266–73.

  10. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the ass ociation between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997 Oct 22–29;278(16):1349–56.

  11. National Health Statistics and Medical Records Division (CU). Anuario Estadístico de Salud 2015 [Internet]. Havana: Ministry of Public Health (CU); 2016 Apr 22 [cited 2017 Mar 27]. Available from: http://fi les.sld.cu/dne/ files/2016/04/Anuario_2015_electronico-1 .pdf. Spanish.

  12. National Health Statistics and Medical Records Division (CU). Anuario Estadístico de Salud 2009 [Internet]. Havana: Ministry of Public Health (CU); 2010 [cited 2017 Mar 27]. 243 p. Available from: http://fi les.sld.cu/dne/fi les/2010/04/anuario -2009e3.pdf. Spanish.

  13. Llibre J. Prevenir la enfermedad de Alzheimer. Havana: Editorial Científi co-Técnica; 2009. Spanish.

  14. Llibre JJ, Valhuerdi A, Calvo M, García RM, Guerra M, Laucerique T, et al. Dementia and other chronic diseases in older adults in Havana and Matanzas: the 10/66 study in Cuba. MEDICC Rev. 2011Oct;13(4):30–7.

  15. Llibre JJ, Fernández Y, Marcheco B, Contreras N, López AM, Otero M. Prevalence of Dementia and Alzheimer’s Disease in a H avana Municipality: A Community-Based Study among Elderly Residents. MEDICC Rev. 2009 Apr;11(2):29–35.

  16. Llibre Rodríguez J, Valhuerdi A, Sánchez II, Reyna C, Guerra MA, Copeland JR, et al. The prevalence, correlates and impact of dementia in Cuba. A 10/66 group population-based survey. Neuroepidemiology. 2008;31(4): 243–51.

  17. Llibre-Rodríguez JJ, Valhuerdi-Cepero A, López- Medina AM, Noriega-Fernández L, Porto-Álvarez R, Guerra-Hernández MA, et al. Cuba’s Aging and Alzheimer Longitudinal Study. MEDICC Rev. 2017 Jan;19(1):31–5.

  18. Teruel BM, Rodríguez JJ, McKeigue P, Mesa TC, Fuentes E, Cepero AV, et al. Interactions between genetic admixture, ethnic identity , APOE genotype and dementia prevalence in an admixed Cuban sample; a cross-sectional population survey and nested case–control study. BMC Med Genet. 2011 Mar 24;12:43. DOI: 10.1186/1471- 2350-12-43.

  19. Llibre JJ. Envejecimiento y demencia: implicaciones para la comunidad científi ca, la salud pública y la sociedad cubana. Anales Aca d Ciencias Cuba. 2012;2(2). Spanish.

  20. Prince M, Acosta D, Ferri CP, Guera M, Huang Y, Llibre Rodríguez JJ, et al. Dementia incidence and mortality in middle-incom e countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study. Lancet. 2012 Jul 7;380(9836):50–8.

  21. Eikelenboom P, van Exel E, Veerhuis R, Rozemuller AJ, van Gool WA, Hoozemans JJ. Innate immunity and the etiology of late-onset Alzheimer’s disease. Neurodegener Dis. 2012;10(1– 4):271–3.

  22. Bouras C, Riederer BM, Kövari E, Hof PR, Giannakopoulos P. Humoral immunity in brain aging and Alzheimer’s disease. Brain Res Brain Re s Rev. 2005 Jun;48(3):477–87.

  23. Levin EC, Acharya NK, Han M, Zavareh SB, Sedeyn JC, Venkataraman V, et al. Brain-reactive autoantibodies are nearly ubiquitous in human sera and may be linked to pathology in the context of blood-brain barrier breakdown. Brain Res. 2010 Jul 23;1345:221–32.

  24. D’Andrea MR. Evidence linking neuronal cell death to autoimmunity in Alzheimer’s disease. Brain Res. 2003 Aug 22;982(1):19–30.

  25. Nagele R G, Clifford PM, Siu G, Levin EC, Acharya NK, Han M, et al. Brain-reactive autoantibodies prevalent in human sera increase intra neuronal amyloid-beta(1–42) deposition. J Alzheimers Dis. 2011;25(4):605–22.

  26. Gruden MA, Davidova TB, Malisauskas M, Sewell RD, Voskresenskaya NI, Wilhem K, et al. Differential neuroimmune markers to the onset of Alzheimer’s disease neurodegeneration and dementia: autoantibodies to Abeta ((25–35)) oligomers, S100b and neurotransmitters. J Neuroimmunol. 2007 May;186(1–2):181–92.

  27. Mor F, Izak M, Cohen IR. Identifi cation of aldolase as a target antigen in Alzheimer’s disease. J Immunol. 2005 Sep 1;175(5):3439–45.

  28. H atzifi lippou E, Koutsouraki E, Banaki T, Traka M, Costa VG, Baloyannis SJ. Antibodies against GM1 in demented patients. Am J Alzheimer s Dis Other Demen. 2008 Jun–Jul;23(3):274–9.

  29. Kankaanpaä J, Turunen SP, Moilanen V, Hörkkö S, Remes AM. Cerebrospinal fl uid antibodies to oxidized LDL are increased in Alzheimer’s d isease. Neurobiol Dis. 2009 Mar;33(3):467–72.

  30. Kellner A, Matschke J, Bernreuther C, Moch H, Ferrer I, Glatzel M. Autoantibodies against betaamyloid are common in Alzheimer’s disease and help control plaque burden. Ann Neurol. 2009 Jan;65(1):24–31.

  31. Brettschneider S, Morgenthaler NG, Teipel SJ, Fischer-Schulz C, Bürger K, Dodel R, et al. Decreased serum amyloid beta (1–42) autoantibody l evels in Alzheimer’s disease, determined by a newly developed immuno-precipitation assay with radiolabeled amyloid beta(1–42) peptide. Biol Psychiatry. 2005 Apr 1;57(7):813–6.

  32. Nath A, Hall E, Tuzova M, Dobbs M, Jons M, Anderson C, et al. Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer’s dis ease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development. Neuromolecular Med. 2003;3(1):29–39.

  33. Butterfi eld DA, Swomley AM, Sultana R. Amyloid beta-peptide (1–42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid Redox Signal. 2013 Sep 10;19(8):823–35.

  34. Walker LC, Jucker M. Neurodegenerative diseases: expanding the prion concept. Annu Rev Neurosci. 2015 Jul 8;38:87–103.

  35. Colasanti T, Barbati C , Rosano G, Malorni W, Ortona E. Autoantibodies in patients with Alzheimer’s disease: pathogenetic role and potential u se as biomarkers of disease progression. Autoimmun Rev. 2010 Oct;9(12):807–11.

  36. Jack CR Jr, Bernstein MA, Borowski BJ, Gunter JL, Fox NC, Thompson PM, et al. Update on the magnetic resonance imaging core of the Alzheimer’ s disease neuroimaging initiative. Alzheimers Dement. 2010 May;6(3):212–20.

  37. Kantarci K. Molecular imaging of Alzheimer disease pathology. Am J Neuroradiol. 2014 Jun;35(6 Suppl):S12–7.

  38. Blennow K, Dubois B, Fagan A M, Lewczuk P, de Leon MJ, Hampel H. Clinical utility of cerebrospinal fl uid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement. 2015 Jan;11(1):58–69.

  39. Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013 Feb;12(2):207–16.

  40. Wenham PR, Price WH, Blandell G. Apolipoprotein E genotyping by one-stage PCR. Lancet. 1991 May 11;337(8750):1158–9.

  41. Suárez VM, Fernández Y, López Edel C, Clarke DH, Bobes MA, Riverón AM, et al. Apolipoprotein E alleles in Cuban patients with mild cognitive impairment. Am J Alzheimers Dis Other Demen. 2014 May;29(3):236–41.

  42. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–94.

  43. Coit P, Ognenovski M, Gensterblum E, Maksimowicz- McKinnon K, Wren JD, Sawalha AH. Ethnicity-specifi c epigenetic variation in naive CD4+ T cells and the susceptibility to autoimmunity. Epigenetics Chromatin. 2015 Nov 24;8:49.

  44. Eric sson C, Peredo I, Nistér M. Optimized protein extraction from cryopreserved brain tissue samples. Acta Oncol. 2007;46(1):10–20.

  45. Dale RC, Candler PM, Church AJ, Wait R, Pocock JM, Giovanni J. Neuronal surface glycolytic enzymes are autoantigen targets in post-streptococcal autoimmune CNS disease. J Neuroimmunol. 2006 Mar;172(1–2):187–97.

  46. Crowt her JR. Methods in Molecular Biology. The ELISA guide book. Vol. 42. New York: Humana Press; 2009. 566 p.

  47. Vadas z Z, Haj T, Kessel A, Toubi E. Age-related autoimmunity. BMC Med. 2013 Apr 4;11:94.

  48. Franc o-Marina F, García-González JJ, Wagner- Echeagaray F, Gallo J, Ugalde O, Sánchez-García S, et al. The Mini-mental State Examination revisited: ceiling and fl oor effects after score adjustment for educational level in an aging Mexican population. Int Psychogeriatr. 2010 Feb;22(1):72–81.

  49. Hanley JA , McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology. 1983 Sep;148(3):839–43.

  50. Cerda J, Cifuentes L. [Using ROC curves in clinical investigation: theoretical and practical issues]. Rev Chilena Infectol. 2012 Apr;29(2):138– 41. Spanish.

  51. Douglas J N, Gardner LA, Levin MC. Antibodies to an intracellular antigen penetrate neuronal cells and cause deleterious effects. J Clin Cell Immunol. 2013 Jan 30;4(1).

  52. Dodel R, Balakrishnan K, Keyvani K, Deuster O, Neff F, Andrei-Selmer LC, et al. Naturally occurring autoantibodies against beta-amyloid: investigating their role in transgenic animal and in vitro models of Alzheimer’s disease. J Neurosci. 2011 Apr 13;31(15):5847–54.

  53. Gustaw-Ro thenberg KA, Siedlak SL, Bonda DJ, Lerner A, Tabaton M, Perry G, et al. Dissociated amyloid-beta antibody levels as a serum biomarker for the progression of Alzheimer’s disease: a population-based study. Exp Gerontol. 2010 Jan; 45(1):47–52.

  54. Storace D , Cammarata S, Borghi R, Sanguineti R, Giliberto L, Piccini A, et al. Elevation of {beta}- amyloid 1–42 autoantibodies in the blood of amnestic patients with mild cognitive impairment. Arch Neurol. 2010 Jul;67(7):867–72.

  55. Klaver AC , Coffey MP, Smith LM, Bennett DA, Finke JM, Dang L, et al. ELISA measurement of specifi c non-antigen-bound antibodies to Abeta1-42 monomer and soluble oligomers in sera from Alzheimer’s disease, mild cognitively impaired, and noncognitively impaired subjects. J Neuroinfl ammation. 2011 Aug 9;8:93.

  56. Maftei M, Thurm F, Schnack C, Tumani H, Otto M, Elbert T, et al. Increased levels of antigenbound beta-amyloid autoantibodies in serum and cerebrospinal fl uid of Alzheimer’s disease patients. PLoS One. 2013 Jul 18;8(7):e68996.

  57. Mruthinti S, Buccafusco JJ, Hill WD, Waller JL, Jackson TW, Zamrini EY, et al. Autoimmunity in Alzheimer’s disease: increased levels of circulating IgGs binding Abeta and RAGE peptides. Neurobiol Aging. 2004 Sep;25(8):1023–32.

  58. Tuohy VK, Kinkel RP. Epitope spreading: a mechanism for progression of autoimmune disease. Arch Immunol Ther Exp (Warsz). 2000;48(5):347–51.

  59. Weisman D , Hakimian E, Ho GJ. Interleukins, infl ammation, and mechanisms of Alzheimer’s disease. Vitam Horm. 2006;74:505–30.

  60. Leon AC, Davis LL, Kraemer HC. The role and interpretation of pilot studies in clinical research. J Psychiatr Res. 2011 May;45(5):626–9.




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