Neurología Cognitiva.pósters

Bridging Science and Care: 14 Years of Genetic and Biomarker Research in Neurodegenerative Diseases at an Argentine Memory Clinic

2025-12-24T00:00:00Z

Bridging Science and Care: 14 Years of Genetic and Biomarker Research in Neurodegenerative Diseases at an Argentine Memory Clinic Surace, Ezequiel Ignacio; Romorini, Leonardo; Marazita, Mariela Claudia; Clas, Giulia Solange; Massazza, Victoria; Alvarez, María Florencia; Avendaño, Daniel; Itzcovich, Tatiana; Martinetto, Horacio Understanding the biological and genetic landscape of neurodegenerative diseases in diverse populations deepens our insight into complex pathophysiological mechanisms. Our laboratory, established 14 years ago in Buenos Aires, Argentina, serves as a regional hub for Latin America, focusing on familial and sporadic cases of Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). We were among the first in the region to incorporate cerebrospinal fluid AD biomarker analysis into clinical diagnostics. Our research includes genetic counseling, the study of novel genetic variants, and the development of patient-derived cell models using induced pluripotent stem cell technology. In this talk, we will discuss the challenges of staying at the forefront of technological advancements and underscore the importance of international collaboration in advancing both local and global knowledge.

Functional validation of the PSEN1 R358P and PSEN1 T119I variants in Alzheimer's Disease: an in vitro study

2025-12-23T00:00:00Z

Functional validation of the PSEN1 R358P and PSEN1 T119I variants in Alzheimer's Disease: an in vitro study García Chialva, Diego; Cifarelli, Diego; Isaja, Luciana; Apecetche, Manuela; Martínes Ojeda, Laura; Itzcovich, Tatiana; Chrem Méndez, Patricio Alexis; Sevlever, Gustavo Emilio; Scassa, Maria; Surace, Ezequiel Ignacio; Romorini, Leonardo Background Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia worldwide. It is characterized by progressive neuronal degeneration and the accumulation of beta‐amyloid plaques (Aβ) and neurofibrillary tangles (NFT) in the brain. AD manifests in sporadic AD (sAD) and familial AD (fAD). fAD is associated with inherited genetic mutations affecting amyloid precursor protein (APP) processing, involving genes such as APP, PSEN1, and PSEN2. Method The identification of two novel PSEN1 variants, p.T119I and p.R358P in early‐onset AD patients at FLENI provided a unique opportunity to study their possible implications in fAD. Notably, the patient harboring the PSEN1 R358P variant also carried a novel SORL1 variant (Gly1536Asp). Noteworthy, genetic variants in SORL1 are now considered a major AD risk factor. To evaluate the role of these two novel PSEN1 variants in APP processing, we developed a cellular model using PSEN1 Knock‐Out (KO) HEK293T cells created through CRISPR/Cas9 technology. We assessed the Aβ 42 /Aβ 40 ratio (AD biomarker) in the supernatant of PSEN1 KO‐cells transfected with expression vectors coding for APP and either wild‐type PSEN1, the novel PSEN1 variants or PSEN1 A246E (a known pathogenic mutation). Result We observed a significant (p <0.05) increase in the Aβ 42 /Aβ 40 ratio in HEK293T cells transfected with PSEN1 A246E or PSEN1 R358P plasmids and a slight trend towards an increase in cells transfected with PSEN1 T119I vector. In the case of PSEN1 R358P‐transfected cells, the increase in the Aβ 42 /Aβ 40 ratio observed was primarily due to the decrease in Aβ 40 levels in the supernatant. Conclusion These findings suggest a potential pathogenic role for the PSEN1 R358P variant in fAD, independent of the co‐occurring SORL1 mutation.

CADASIL Argentine Registry: Study Design and Preliminary Data

2024-01-01T00:00:00Z

CADASIL Argentine Registry: Study Design and Preliminary Data Ardohain Cristalli, Carolina Agata; Rosales, Julieta Soledad; Gonzalez, Fabio; Selvaggi, Valentin; Alonso, Julián Martín; López, Juan Ignacio; Aguilar, Martín Santiago; Kauffman, Marcelo; Saks, Danit G.; Allegri, Ricardo Francisco; Sevlever, Gustavo Emilio; Chaves, Hernán; Cristalli, Diana Olga; Calandri, Ismael Luis Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common hereditary small vessel disease, leads to early-onset stroke and vascular cognitive impairment (VCI). Despite its importance, data from Latin America remain scarce. The CADASIL Argentine registry (CADASILAr) was created to harmonize clinical data, promote international collaboration, and provide a reproducible, longitudinal framework to study disease progression and expand to neighboring countries. This study aims to present the cohort design and preliminary results from the cross-sectional phase. Method: CADASILAr was developed to document demographic, clinical, imaging, and genetic features of CADASIL patients and to explore factors associated with disease progression and cognitive decline in an Argentinian multisite cohort. The study includes two phases: (1) a cross-sectional phase (CADASILAR-C) and (2) a longitudinal phase (CADASILAR-Long), following adults aged ≥18 years with genetically confirmed or suspected CADASIL. Variables collected include demographics, symptom onset, clinical features, neuroimaging, genetic data, and vascular risk factors. The study also examines socio-economic disparities, integrates biobanks, and harmonizes data collection with international CADASIL and dementia registries. Longitudinal followups are planned annually over 5 years (Figure 1), with cognitive batteries aligned with international cohorts and a brain donation program to establish a CADASIL brain bank in Argentina. Result: Preliminary data from 90 patients (50% female) show a mean age of 43.8±11.9 years, with family history in 91.6% (Figure 2). The most common clinical presentations were cerebrovascular events (72.9%), cognitive impairment (56.7%), and migraine (69%). The most frequent comorbidities included hypertension (64%) and dyslipidemia (55%). Among 86 confirmed cases, 63 were diagnosed through genetic testing and 20 through skin biopsy. Genetic analysis identified cysteine-altering NOTCH3 mutations in all confirmed cases, predominantly affecting epidermal growth factor-like repeats (Figure 3). Of the 33 patients assessed with the MMSE, the median score was 28 (IQR: 22–29). Conclusion: CADASILAr is the first systematic effort to study this disease in Latin America and the twelfth global CADASIL registry. By integrating baseline and longitudinal data, it offers a robust platform to investigate genetic, neuroimaging, and cognitive outcomes while fostering international collaborations to advance research and understanding of CADASIL.

2- Cognitive Impairment and Dementia in Latin American Individuals with Parkinsonism and Parkinson’s Disease: A 10/66 Dementia Research Group Study (Ana Luisa Sosa)

2024-09-01T00:00:00Z

2- Cognitive Impairment and Dementia in Latin American Individuals with Parkinsonism and Parkinson’s Disease: A 10/66 Dementia Research Group Study (Ana Luisa Sosa) Sosa, Ana Luisa; Khan, N.; Arruabarrena, Micaela María; Kim, D.J.; Jiang, M.; Llibre-Guerra, Jorge J.; Rodriguez-Salgado, A.M.; Acosta, I.; Acosta, D.; Jimenez-Velasquez, I.Z.; Guerra, M.; Salas, A.; López-Contreras, R.; Dhara, Santana; Hesse, H.; Tanner, C.; Prina, M.; Llibre-Guerra, J.J.; 10/66 Dementia ResearchGroup