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DTSTAMP:20260404T224641Z
UID:1715331600@ist.ac.at
DTSTART:20240510T110000
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DESCRIPTION:Speaker: Mariano Ignacio Gabitto\nhosted by Lora Sweeney\nAbstr
 act: Histopathology studies of Alzheimer’s disease (AD) have long noted 
 progressive\, and stereotyped changes across numerous brain regions\, but 
 the underlying molecular and cellular mechanisms that cause AD and facilit
 ate its progression remain unknown or are only coarsely understood\, hampe
 ring efforts to treat or cure the disease. To uncover these mechanisms\, 
 we characterized the transcriptomic and epigenetic landscapes of AD from t
 he middle temporal gyrus\, and prefrontal cortex by applying single nucleu
 s RNA and ATAC sequencing to ~8 million nuclei isolated in 84 aged donors 
 that span the histopathological and cognitive disease spectrums as part of
  the broader Seattle AD Brain Cell Atlas (SEA-AD) effort. We leveraged mac
 hine learning approaches to hierarchically define ~130 highly resolved tra
 nscriptional cell types borrowing from the BRAIN initiatives’ neurotypic
 al reference. We utilized Bayesian statistical models to define a continuo
 us scale of pathological progression using multiple measures of pathologic
 al proteins\, and cellular populations. We aligned donors according to dis
 ease severity\, akin to the pseudotime score commonly used to align cells 
 in neurodevelopment.These tools enabled characterization of cell type abun
 dance\, gene expression\, and chromatin accessibility differences associat
 ed with AD. Our comprehensive molecular atlas identified specific neuronal
  and non-neuronal subsets\, having altered abundances\, gene expression\, 
 and/or chromatin accessibility\, and suggesting they may be selectively vu
 lnerable to disease processes. Their differentially expressed genes and ac
 cessible chromatin regions provided new clues to the molecular pathways th
 at underpin AD. We integrated with SEA-AD 10 external datasets that had ap
 plied snRNA-seq to 4.3 million cells from the DLPFC of 780 donors. We used
  this as replication cohorts and identified cellular changes consistently 
 associated with AD. Finally\, we created mapping algorithms to map publish
 ed single cell data sets to our taxonomical reference. These mapping tools
  create a resource for the research community to align newly profiled cell
 s to a common reference frame. All data sets and mapping algorithms are av
 ailable sea-ad.org.
LOCATION:Moonstone Seminar room C \, ISTA
ORGANIZER:judit.gazsi@ist.ac.at
SUMMARY:Mariano Ignacio Gabitto: A multimodal Atlas of Alzheimer's Disease 
 to Arrange Molecular and Cellular Changes Along Disease Progression
URL:https://talks-calendar.ista.ac.at/events/4922
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