Neurología Cognitiva.pósters

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

2026-05-19T14:58:36Z

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

2026-02-19T13:41:59Z

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)

2025-10-22T16:49:59Z

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

Experts envision a valuable role for tau-PET in clinical practiceand drug trials

2025-04-15T15:37:19Z

Experts envision a valuable role for tau-PET in clinical practiceand drug trials Vermeiren, Marie R.; Calandri, Ismael Luis; van der Flier, Wiesje M.; van de Giessen, Elsmarieke; Ossenkoppele, Rik Background: Recent advancements in Alzheimer’s disease (AD) biomarker researchand AD drug trials prompt reflection on the value and appropriate use of tau-PET infuture clinical practice and trials. We therefore conducted a survey among dementiaand PET experts worldwide to investigate how they envision the future role of tau-PETin clinical practice and trials.Method: An online survey was distributed to dementia clinicians and researchers whowere invited to participate through personalized emails, social media channels and/orpresentations at relevant conferences. With this approach we intended to recruitparticipants from different countries with diverse backgrounds and expertise. Thesurvey questions explored experts’ opinions on the value of tau-PET in clinical practiceand in drug development and trials. We used a mix of multiple choice questions,statements with a 5-point Likert scale (“strongly disagree” to “strongly agree”) and afew open questions.Result: In total 269 dementia experts, comprising 144 clinicians and 121 researchers,covering six continents completed the survey (Figure 1). The vast majority (90%)fosters a positive attitude on the added value of tau-PET in clinical practice, particularlyfor staging, diagnosing, monitoring and prognostication in a cognitively impairedmemory clinic population (Figure 2). When confronted with clinical case vignettes, ourfindings suggest that a tau-PET scan is perceived particularly useful in patients withan atypical presentation (78%) or suspicion of mixed pathology (66%) and less usefulin a typical AD case (25%). Experts are confident that a tau-PET scan could influencepatient management in current practice (median 4 “agree” [IQR 4-5]) and this wouldincrease when effective disease-modifying treatments are available (median 4 “agree”[IQR 3-4]) (Figure 2). Experts anticipate an important role for tau-PET for participantselection (76-100%) and measuring endpoints (75-97%), in both anti-amyloid andanti-tau drug trials (Figure 3).