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Almeida, Maria Camila ; Eger, Sarah J. ; He, Caroline ; Audouard, Morgane ; Nikitina, Arina ; Glasauer, Stella M. K. ; Han, Dasol ; Mejia-Cupajita, Barbara ; Acosta-Uribe, Juliana ; Villalba-Moreno, Nelson David ; Littau, Jessica Lisa ; Elcheikhali, Megan ; Rivera, Erica Keane ; Carrettiero, Daniel Carneiro ; Villegas-Lanau, Carlos Andres ; Sepulveda-Falla, Diego ; Lopera, Francisco ; Kosik, Kenneth S.

• Tipo de documento: Artigo Científico
• Fonte: NEURON; v. 112, n. 11, p. 25-pg., 2024-06-05.

Resumo

Highly penetrant autosomal dominant Alzheimer's disease (ADAD) comprises a distinct disease entity as compared to the far more prevalent form of AD in which common variants collectively contribute to risk. The downstream pathways that distinguish these AD forms in specific cell types have not been deeply explored. We compared single -nucleus transcriptomes among a set of 27 cases divided among PSEN1 - E280A ADAD carriers, sporadic AD, and controls. Autophagy genes and chaperones clearly defined the PSEN1 -E280A cases compared to sporadic AD. Spatial transcriptomics validated the activation of chaperone -mediated autophagy genes in PSEN1- E280A. The PSEN1 -E280A case in which much of the brain was spared neurofibrillary pathology and harbored a homozygous APOE3 -Christchurch variant revealed possible explanations for protection from AD pathology including overexpression of LRP1 in astrocytes, increased expression of FKBP1B , and decreased PSEN1 expression in neurons. The unique cellular responses in ADAD and sporadic AD require consideration when designing clinical trials. (AU)

• Processo FAPESP: 19/22708-1 - A Co-chaperona Bag2: "liquid droplets" e sua importância para a doença de Alzheimer
• Beneficiário: Daniel Carneiro Carrettiero
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 19/22819-8 - Análise de transcriptoma de pacientes com mutação para TREM2: implicações para o entendimento da disfunção da microglia como fator de risco para patologia de Alzheimer
• Beneficiário: Maria Camila Almeida
• Modalidade de apoio: Bolsas no Exterior - Pesquisa