In Memoriam: Francisco Javier Lopera RestrepoFrancisco Javier Lopera Restrepo passed away on September 10, 2024, a great loss for his family, friends, and collaborators, for all of science, and, particularly, for neurosciences in Latin America. He leaves the advances brought by his studies as well as a great legacy that will certainly have important developments to be carried out by the large number of high-quality disciples he left behind.
Much will be written about the importance of Francisco Lopera for advancing knowledge about Alzheimer's disease. There are aspects that may be considered more important for the entire research community, especially for those from low- and middle-income countries.
Almost all Francisco Lopera's publications are about autosomal-dominant Alzheimer's disease, which was described in 19871. Collaboration with a large group of investigators led to the discovery of the E280A mutation of presenilin 1 in 19952. From his careful studies of this family, he was able to obtain enough data to transform it into the world's largest autosomal-dominant Alzheimer's disease kindred, which made possible to make contributions to the knowledge of several steps of the evolution of Alzheimer's disease.
Two of them are highlighted here. The first one made it possible to verify the first changes in biomarkers, the time interval between these changes, and the first symptoms hallmarking the onset of dementia. These discoveries revealed that the interval between changes in biomarkers and dementia is greater than 20 years3,4.
The second one is the case of the patient Aliria, who, having the E280A mutation of presenilin 1, did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset5. Aliria died at the age of 77 years without dementia, when the average age at which dementia occurs in the disease caused by this mutation is about 49 years5,6. The neuropathological examination confirmed the presence of unusually high brain amyloid levels and limited tau and neurodegenerative measurements6, which had already been revealed by amyloid-positron emission tomography (PET) and tau-PET performed years before5. The patient had two copies of the APOE3 Christchurch (R136S) mutation, which points to the role of APOE in the pathogenesis, treatment, and prevention of Alzheimer's disease5,6.
These and many of his other contributions were rightly awarded, most notably the Bengt Winblad Lifetime Achievement Award in 2020, from the Alzheimer's Association, and the Potamkin Prize (often called the "Nobel Prize of Alzheimer's research"), from the American Academy of Neurology (AAN) and the American Brain Foundation (ABF), in 2024.
In addition to the importance of these studies for scientific knowledge, there is much to be learned from their studies by all researchers in Latin America.
First, tenacity, persistence, maintaining focus, and the firm conviction that this determination would bring more and more important discoveries. Between the first publication on this disease and the Aliria case, 32 years of continued studies passed.
Second, but no less important, he had good collaborators among his colleagues and students and chose the best international collaborators, in whom he could trust and who did not look at a researcher from a low- and middle-income country as a mere data provider to enrich their own research. Despite the depth of his research that he would not have achieved if he had not had international collaboration, Francisco Lopera always remained the main researcher and unquestionable leader of his publications.
According to Natalia Acosta-Baena, one of his closest collaborators, he was always concerned with improving the quality of life of the patients who were being under study by his group, and he kept "a balance between consent without falling into coercion" while dealing with this vulnerable population.
Like many neurologists of his time, Francisco Lopera began studying dementia through studies in neuropsychology, as can be seen from some articles on these topics among his first publications7,8, and during his career, he had kept an in-depth knowledge of cognitive and behavioral neurology.
Francisco Lopera was a member of the Advisory Board of Dementia & Neuropsychologia, and together with his group, he published a paper entitled "Genetics of dementia: insights from Latin America9," a relevant contribution to the field and to our journal.
Finally, Francisco Lopera could have been nominated for the Nobel Prize, which would have been another of his formidable examples for the entire community of neuroscientists in Latin America and abroad.
REFERENCES
- 1 Cornejo W, Lopera F, Uribe CS, Salinas M. Descripción de una familia con demencia presenil tipo Alzheimer. Acta Méd Colomb. 1987;12(2):55-61.
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2 Alzheimer's Disease Collaborative Group. The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet. 1995;11(2):219-22. https://doi.org/10.1038/ng1095-219
» https://doi.org/10.1038/ng1095-219 -
3 Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, Jaramillo-Elorza MC, Moreno S, Aguirre-Acevedo DC, et al. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study. Lancet Neurol. 2011;10(3):213-20. https://doi.org/10.1016/S1474-4422(10)70323-9
» https://doi.org/10.1016/S1474-4422(10)70323-9 -
4 Reiman EM, Quiroz YT, Fleisher AS, Chen K, Velez-Pardo C, Jimenez-Del-Rio M, et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study. Lancet Neurol. 2012;11(12):1048-56. https://doi.org/10.1016/S1474-4422(12)70228-4
» https://doi.org/10.1016/S1474-4422(12)70228-4 -
5 Arboleda-Velasquez JF, Lopera F, O'Hare M, Delgado-Tirado S, Marino C, Chmielewska N, et al. Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019;25(11):1680-3. https://doi.org/10.1038/s41591-019-0611-3
» https://doi.org/10.1038/s41591-019-0611-3 -
6 Sepulveda-Falla D, Sanchez JS, Almeida MC, Boassa D, Acosta-Uribe J, Vila-Castelar C, et al. Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer's dementia. Acta Neuropathol. 2022;144(3):589-601. https://doi.org/10.1007/s00401-022-02467-8
» https://doi.org/10.1007/s00401-022-02467-8 - 7 Lopera F. Procesamiento de caras: bases neurológicas, trastornos y evaluación [Processing of faces: neurological bases, disorders and evaluation]. Rev Neurol. 2000;30(5):486-90.
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8 Sierra M, Lopera F, Lambert MV, Phillips ML, David AS. Separating depersonalisation and derealisation: the relevance of the "lesion method". J Neurol Neurosurg Psychiatry. 2002;72(4):530-2. https://doi.org/10.1136/jnnp.72.4.530
» https://doi.org/10.1136/jnnp.72.4.530 -
9 Ramos C, Aguillon D, Cordano C, Lopera F. Genetics of dementia: insights from Latin America. Dement Neuropsychol. 2020;14(3):223-36. https://doi.org/10.1590/1980-57642020dn14-030004
» https://doi.org/10.1590/1980-57642020dn14-030004
