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Aroca Molina, L. (2025). Beyond realism and constructivism: Alzheimer’s as a resfactum in a relational ontology of biomedical entities. Discusiones Filosóficas, 26(47). https://doi.org/10.17151/difil.2025.26.47.7
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Abstract
This article challenges the dichotomy between realism and constructivism in the philosophy of science, arguing that it is insufficient for understanding biomedical entities such as Alzheimer’s disease. From this limitation, a new concept termed resfactum is proposed to account for the mode of existence of Alzheimer’s. Through it, the aim is to transcend the opposition between the “discovered” and the “constructed,” in order to understand Alzheimer’s as an entity that simultaneously articulates independent causal mechanisms, materiality embodied in human bodies, and intelligibility mediated socially and historically. To illustrate this proposal, the case of the PSEN1-E280A mutation (Paisa mutation), responsible for a form of early-onset hereditary Alzheimer’s, is analyzed. This analysis shows that, although the molecular processes in this condition operate independently of human categorization, Alzheimer’s exists in human brains and is socially configured through diagnostic frameworks, analytical technologies, and historical and identity narratives. Thus, the article concludes by arguing that resfactum offers a useful ontological framework for the analysis of biomedical entities from their multiple dimensions.
References
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Bhaskar, R. (2008). A Realist Theory of Science. Routledge.
Bhaskar, R. (1979). The Possibility of Naturalism. The Harvester Press.
Bloom, G. S. (2014). Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurology, 71(4), 505-508.
Brandom, R. (1994). Making it explicit: Reasoning, representing, and discursive commitment. Harvard University Press.
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 261(5123), 921-923.
Copérnico, N. (1543). De revolutionibus orbium coelestium [Sobre las revoluciones de las esferas celestes]. Núremberg: Johannes Petreius.
Darwin, C. (1859). On the origin of species by means of natural selection, or the preservation of favoured races in the struggle for life. John Murray.
Epstein, S. (1996). Impure science: AIDS, activism, and the politics of knowledge. University of California Press.
Ferrer, I. (2024). Brain aging and Alzheimer’s disease: A perspective from non-human primates. Aging, 16(20), 13145–13171. https://doi.org/10.18632/aging.206143
First, M. B. (2010). Paradigm shifts and the development of the diagnostic and statistical manual of mental disorders: past experiences and future aspirations. The Canadian Journal of Psychiatry, 55(11), 692-700.
Finch, C. E., & Austad, S. N. (2012). Primate aging and Alzheimer’s disease: From monkeys to humans and back. Pathobiology of Aging & Age-related Diseases, 2, 1–11. https://doi.org/10.3402/pba.v2i0.15084
Fox, P. J. (1989). From senility to Alzheimer’s disease: The rise of the Alzheimer’s disease movement. The Milbank Quarterly, 67(1), 58-102
Fraser, B. (2023). Do genes point the way to an Alzheimer’s cure? En Alzheimer’s Disease International, World Alzheimer Report 2023: Reducing dementia risk - never too early, never too late (pp. 68-71). Alzheimer’s Disease International. https://www.alzint.org/resource/world-alzheimer-report-2023/
French, S. (2014). The structure of the world: Metaphysics and representation. Oxford University Press.
Giere, R. N. (2006). Scientific perspectivism. University of Chicago Press.
Guerreiro, R. J., Gustafson, D. R., & Hardy, J. (2012). The genetic architecture of Alzheimer's disease: beyond APP, PSENs and APOE. Neurobiology of aging, 33(3), 437-456.
Hacking, I. (1983). Representing and Intervening. Cambridge University Press.
Hacking, I. (1999). The Social Construction of What?. Harvard University Press.
Hacking, I. (2007). Kinds of people: Moving targets. Proceedings of the British Academy, 151, 285-318.
Hansen, D. V., Hanson, J. E., & Sheng, M. (2021). Microglia in Alzheimer’s disease. The Journal of Cell Biology, 220(4), e202012067.
Hardy, J., & Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science, 297(5580), 353-356.
Haraway, D. J. (1991). Simians, cyborgs, and women: The reinvention of nature. Routledge.
Head, E., Lott, I. T., Wilcock, D. M., & Rabe, A. (2005). Aging in canines and humans: Roles of oxidative stress, β-amyloid, and tau pathology. Neurobiology of Aging, 26(5), 691–699. https://doi.org/10.1016/j.neurobiolaging.2004.09.017
Heneka, M. T., Kummer, M. P., & Latz, E. (2015). Innate immune activation in neurodegenerative disease. Nature Reviews Immunology, 15(7), 463–477.
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., Liu, E., Molinuevo, J. L., Montine, T., Phelps, C., Rankin, K. P., Rowe, C. C., Scheltens, P., Siemers, E., Snyder, H. M., … Silverberg, N. (2018). NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia, 14(4), 535-562.
Jack, C. R., Andrews, J. S., Beach, T. G., Bennett, D. A., Blennow, K., Carrillo, M. C., ... et al. (2024). Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimer’s & Dementia, 20(8), 5143–5169.
Karran, E., & De Strooper, B. (2022). The amyloid cascade hypothesis: Are we poised for success or failure? Nature Reviews Drug Discovery, 21(5), 306–318.
Kendig, C. E. (Ed.). (2016). Natural kinds and classification in scientific practice. Routledge.
Kendler, K. S., & Zachar, P. (2010). Social construction and psychopathology: Confidence and caution. In P. Zachar, K. S. Kendler, & J. Parnas (Eds.), Toward a philosophical approach to psychiatry: The collected papers of Kenneth S. Kendler (pp. 249-263). Oxford University Press.
Khalidi, M. A. (2013). Natural categories and human kinds: Classification in the natural and social sciences. Cambridge University Press.
Kuhn, T. S. (1962). The Structure of Scientific Revolutions. University of Chicago Press.
Latour, B. (1993). We have never been modern. Harvard University Press.
Latour, B., & Woolgar, S. (1979). Laboratory Life: The Social Construction of Scientific Facts. Sage Publications.
LaFerla, F. M., & Green, K. N. (2012). Animal models of Alzheimer disease. Cold Spring Harbor Perspectives in Medicine, 2(11), a006320. https://doi.org/10.1101/cshperspect.a006320
Ladyman, J., & Ross, D. (2007). Every thing must go: Metaphysics naturalized. Oxford University Press.
Longino, H. E. (2002). The fate of knowledge. Princeton University Press
Lopera, F., Marino, C., Chandrahas, A. S., O’Hare, M., Villalba-Moreno, N. D., Aguillon, D., ... & Quiroz, Y. T. (2023). Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man. Nature medicine, 29(5), 1243-1252.
Maurer, K., Volk, S., & Gerbaldo, H. (1997). Auguste D and Alzheimer’s disease. The lancet, 349(9064), 1546-1549.
Massimi, M. (2018). Four kinds of perspectival truth. Philosophy and Phenomenological Research, 96(2), 342-359.
Maxwell, J. C. (1872). Theory of Heat. Longmans.
Mol, A. (2002). The body multiple: Ontology in medical practice. Duke University Press.
Mukherjee, S. (2010). The emperor of all maladies: A biography of cancer. Scribner.
Mumford, S. (1998). Dispositions. Oxford University Press.
Nagel, T. (1986). The View from Nowhere. Oxford University Press.
Psillos, S. (1999). Scientific Realism: How Science Tracks Truth. Routledge.
Putnam, H. (1975). Mathematics, Matter and Method: Philosophical Papers, Vol. 1. Cambridge University Press.
Price, H. (2011). Naturalism without mirrors. Oxford University Press.
Quiroz, Y. T., Sperling, R. A., Norton, D. J., Baena, A., Arboleda-Velasquez, J. F., Cosio, D., ... & Lopera, F. (2015). Brain imaging and blood biomarker abnormalities in children with autosomal dominant Alzheimer disease. JAMA Neurology, 72(8), 912–919.
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Reiman, E. M., Langbaum, J. B. S., Fleisher, A. S., Caselli, R. J., Chen, K., Ayutyanont, N., ... & Tariot, P. N. (2020). Alzheimer’s Prevention Initiative: A plan to accelerate the evaluation of presymptomatic treatments. The Journal of Prevention of Alzheimer’s Disease, 7(2), 76–84.
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021). Alzheimer’s disease. The Lancet, 397(10284), 1577–1590.
Smith, M. (2020, November 12). Aliria Piedrahíta: Colombian woman with rare gene mutation provides clues to Alzheimer’s resistance. The New York Times.
Strassnig, M. T., & Ganguli, M. (2005, September). About a peculiar disease of the cerebral cortex: Alzheimer’s original case revisited. Psychiatry, 30-33. https://www.researchgate.net/publication/49647477
Vico, G. B. (1995 [1744]). La ciencia nueva. Tecnos.
Vico, G. B. (1999-2000 [1710]). La antiquísima sabiduría de los italianos partiendo de los orígenes de la lengua latina (F. J. Navarro Gómez, Trad.). Cuadernos sobre Vico, 11-12, 443-456.
Walker, L. C., & Jucker, M. (2017). The exceptional vulnerability of humans to Alzheimer’s disease. Trends in molecular medicine, 23(6), 534-545.
Worrall, J. (1989). Structural realism: The best of both worlds? Dialectica, 43(1–2), 99–124.
Woolgar, S. (1988). Science: The very idea. Tavistock Publications.
Zachar, P. (2014). A metaphysics of psychopathology. MIT Press.
Van Fraassen, B. C. (1980). The scientific image. Oxford University Press.
Berger, P., & Luckmann, T. (1966). The Social Construction of Reality: A Treatise in the Sociology of Knowledge. Anchor Books.
Bird, A. (2007). Nature’s metaphysics: Laws and properties. Oxford University Press.
Boyd, R. (1991). Realism, anti-foundationalism, and the enthusiasm for natural kinds. Philosophical Studies, 61(1–2), 127–148.
Bhaskar, R. (2008). A Realist Theory of Science. Routledge.
Bhaskar, R. (1979). The Possibility of Naturalism. The Harvester Press.
Bloom, G. S. (2014). Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurology, 71(4), 505-508.
Brandom, R. (1994). Making it explicit: Reasoning, representing, and discursive commitment. Harvard University Press.
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 261(5123), 921-923.
Copérnico, N. (1543). De revolutionibus orbium coelestium [Sobre las revoluciones de las esferas celestes]. Núremberg: Johannes Petreius.
Darwin, C. (1859). On the origin of species by means of natural selection, or the preservation of favoured races in the struggle for life. John Murray.
Epstein, S. (1996). Impure science: AIDS, activism, and the politics of knowledge. University of California Press.
Ferrer, I. (2024). Brain aging and Alzheimer’s disease: A perspective from non-human primates. Aging, 16(20), 13145–13171. https://doi.org/10.18632/aging.206143
First, M. B. (2010). Paradigm shifts and the development of the diagnostic and statistical manual of mental disorders: past experiences and future aspirations. The Canadian Journal of Psychiatry, 55(11), 692-700.
Finch, C. E., & Austad, S. N. (2012). Primate aging and Alzheimer’s disease: From monkeys to humans and back. Pathobiology of Aging & Age-related Diseases, 2, 1–11. https://doi.org/10.3402/pba.v2i0.15084
Fox, P. J. (1989). From senility to Alzheimer’s disease: The rise of the Alzheimer’s disease movement. The Milbank Quarterly, 67(1), 58-102
Fraser, B. (2023). Do genes point the way to an Alzheimer’s cure? En Alzheimer’s Disease International, World Alzheimer Report 2023: Reducing dementia risk - never too early, never too late (pp. 68-71). Alzheimer’s Disease International. https://www.alzint.org/resource/world-alzheimer-report-2023/
French, S. (2014). The structure of the world: Metaphysics and representation. Oxford University Press.
Giere, R. N. (2006). Scientific perspectivism. University of Chicago Press.
Guerreiro, R. J., Gustafson, D. R., & Hardy, J. (2012). The genetic architecture of Alzheimer's disease: beyond APP, PSENs and APOE. Neurobiology of aging, 33(3), 437-456.
Hacking, I. (1983). Representing and Intervening. Cambridge University Press.
Hacking, I. (1999). The Social Construction of What?. Harvard University Press.
Hacking, I. (2007). Kinds of people: Moving targets. Proceedings of the British Academy, 151, 285-318.
Hansen, D. V., Hanson, J. E., & Sheng, M. (2021). Microglia in Alzheimer’s disease. The Journal of Cell Biology, 220(4), e202012067.
Hardy, J., & Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science, 297(5580), 353-356.
Haraway, D. J. (1991). Simians, cyborgs, and women: The reinvention of nature. Routledge.
Head, E., Lott, I. T., Wilcock, D. M., & Rabe, A. (2005). Aging in canines and humans: Roles of oxidative stress, β-amyloid, and tau pathology. Neurobiology of Aging, 26(5), 691–699. https://doi.org/10.1016/j.neurobiolaging.2004.09.017
Heneka, M. T., Kummer, M. P., & Latz, E. (2015). Innate immune activation in neurodegenerative disease. Nature Reviews Immunology, 15(7), 463–477.
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., Liu, E., Molinuevo, J. L., Montine, T., Phelps, C., Rankin, K. P., Rowe, C. C., Scheltens, P., Siemers, E., Snyder, H. M., … Silverberg, N. (2018). NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia, 14(4), 535-562.
Jack, C. R., Andrews, J. S., Beach, T. G., Bennett, D. A., Blennow, K., Carrillo, M. C., ... et al. (2024). Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimer’s & Dementia, 20(8), 5143–5169.
Karran, E., & De Strooper, B. (2022). The amyloid cascade hypothesis: Are we poised for success or failure? Nature Reviews Drug Discovery, 21(5), 306–318.
Kendig, C. E. (Ed.). (2016). Natural kinds and classification in scientific practice. Routledge.
Kendler, K. S., & Zachar, P. (2010). Social construction and psychopathology: Confidence and caution. In P. Zachar, K. S. Kendler, & J. Parnas (Eds.), Toward a philosophical approach to psychiatry: The collected papers of Kenneth S. Kendler (pp. 249-263). Oxford University Press.
Khalidi, M. A. (2013). Natural categories and human kinds: Classification in the natural and social sciences. Cambridge University Press.
Kuhn, T. S. (1962). The Structure of Scientific Revolutions. University of Chicago Press.
Latour, B. (1993). We have never been modern. Harvard University Press.
Latour, B., & Woolgar, S. (1979). Laboratory Life: The Social Construction of Scientific Facts. Sage Publications.
LaFerla, F. M., & Green, K. N. (2012). Animal models of Alzheimer disease. Cold Spring Harbor Perspectives in Medicine, 2(11), a006320. https://doi.org/10.1101/cshperspect.a006320
Ladyman, J., & Ross, D. (2007). Every thing must go: Metaphysics naturalized. Oxford University Press.
Longino, H. E. (2002). The fate of knowledge. Princeton University Press
Lopera, F., Marino, C., Chandrahas, A. S., O’Hare, M., Villalba-Moreno, N. D., Aguillon, D., ... & Quiroz, Y. T. (2023). Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man. Nature medicine, 29(5), 1243-1252.
Maurer, K., Volk, S., & Gerbaldo, H. (1997). Auguste D and Alzheimer’s disease. The lancet, 349(9064), 1546-1549.
Massimi, M. (2018). Four kinds of perspectival truth. Philosophy and Phenomenological Research, 96(2), 342-359.
Maxwell, J. C. (1872). Theory of Heat. Longmans.
Mol, A. (2002). The body multiple: Ontology in medical practice. Duke University Press.
Mukherjee, S. (2010). The emperor of all maladies: A biography of cancer. Scribner.
Mumford, S. (1998). Dispositions. Oxford University Press.
Nagel, T. (1986). The View from Nowhere. Oxford University Press.
Psillos, S. (1999). Scientific Realism: How Science Tracks Truth. Routledge.
Putnam, H. (1975). Mathematics, Matter and Method: Philosophical Papers, Vol. 1. Cambridge University Press.
Price, H. (2011). Naturalism without mirrors. Oxford University Press.
Quiroz, Y. T., Sperling, R. A., Norton, D. J., Baena, A., Arboleda-Velasquez, J. F., Cosio, D., ... & Lopera, F. (2015). Brain imaging and blood biomarker abnormalities in children with autosomal dominant Alzheimer disease. JAMA Neurology, 72(8), 912–919.
Quiroz, Y., & Sepúlveda-Falla, D. (2022, 4 de agosto). El cerebro de Aliria, un legado que desafía al alzhéimer. Universidad de Antioquia - UdeA Noticias. https://www.udea.edu.co/wps/portal/udea/web/inicio/udea-noticias/udea-noticia/!ut/p/z0/fYy9DsIwEINfhaVjdSGUAGPFgIQYGBBqb0GnNioHIdefgHh8UlhgYbHsT7YBoQD09OCGAosnF3OJ5rRcrfU0z9ROmcyo3Oyz-UJvZoejgi3g_0J84EvXYQ5YiQ_2GaBopQ_k7rWlRNHwm85ysx8_6sRL4IppSNR77bmWsfWF2froInTcM6XjKqVGBq20hvaK5Quc0X49/
Reiman, E. M., Langbaum, J. B. S., Fleisher, A. S., Caselli, R. J., Chen, K., Ayutyanont, N., ... & Tariot, P. N. (2020). Alzheimer’s Prevention Initiative: A plan to accelerate the evaluation of presymptomatic treatments. The Journal of Prevention of Alzheimer’s Disease, 7(2), 76–84.
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021). Alzheimer’s disease. The Lancet, 397(10284), 1577–1590.
Smith, M. (2020, November 12). Aliria Piedrahíta: Colombian woman with rare gene mutation provides clues to Alzheimer’s resistance. The New York Times.
Strassnig, M. T., & Ganguli, M. (2005, September). About a peculiar disease of the cerebral cortex: Alzheimer’s original case revisited. Psychiatry, 30-33. https://www.researchgate.net/publication/49647477
Vico, G. B. (1995 [1744]). La ciencia nueva. Tecnos.
Vico, G. B. (1999-2000 [1710]). La antiquísima sabiduría de los italianos partiendo de los orígenes de la lengua latina (F. J. Navarro Gómez, Trad.). Cuadernos sobre Vico, 11-12, 443-456.
Walker, L. C., & Jucker, M. (2017). The exceptional vulnerability of humans to Alzheimer’s disease. Trends in molecular medicine, 23(6), 534-545.
Worrall, J. (1989). Structural realism: The best of both worlds? Dialectica, 43(1–2), 99–124.
Woolgar, S. (1988). Science: The very idea. Tavistock Publications.
Zachar, P. (2014). A metaphysics of psychopathology. MIT Press.
