Tau and APP relation in human cerebral organoids with the Swedish mutation

HOLUBIEC, MARIANA; SARGIOTTO DE RAEDEMAEKER; ALLOATTI MATIAS; FALZONE, TOMAS; FERNANDEZ BESSONE, IVAN; SAEZ, TRINIDAD

Congreso; XXXIV Reunión Anual SAN 2019; 2019

Alzheimer disease (AD) is the main neurodegenerative ailment affecting human populations (1,2). Mutations in amyloid precursor protein (APP), which give rise to amyloid-beta (Aβ) when processed, are linked to familial AD. The Swedish (Swe) mutation occurs next to the Aβ region and increases amyloidogenic processing (3). Tau is a microtubule associated protein that belongs to the MAP2 family, it is involved in axonal transport and neurite growth (4). In AD tau is hyper-phosphorylated and aggregated, forming neurofibrillary tangles (5). Alternative splicing produces several tau isoforms, some of which (3R and 4R) are linked to the onset of dementia (6). Until this day the idea of studying tau modifications related to the Swe mutation in a model with human genomics and proteomics has not been fulfilled.We produced human cerebral organoids from induced pluripotent stem cell (IPSC) colonies obtained from a control patient and a patient with the Swe mutation (7). Fully grown and differentiated organoids were processed for further analysis.Using Congo red staining and Aβ, we observed amyloid aggregates in samples with the Swe mutation. Using specific antibodies we observed changes in tau levels in Swe and control organoids as wells as a distinct tau 3R/4R isoform localization in control and Swe samples.All in all, using a human cerebral model, we describe the AD pathology in Swe samples as well as a particular expression of tau isoforms in Swe and control organoids.