Carlo Sala Frigerio

Author Correction: Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer’s disease

Sebastiaan De Schepper, Judy Z. Ge, Annerieke Sierksma, Gerard Crowley et autres

A clerical error occurred during the submission of the final accepted version of this paper, in which draft versions of the source data files were mistakenly uploaded instead of the final, cross-checked versions. As a result, discrepancies arose between the published, correct …

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The amyloid precursor family of proteins in excitatory neurons are essential for regulating cortico-hippocampal circuit dynamics in vivo

Sam Harris, Rikesh M. Rajani, Jana Zünkler, Robert Ellingford et autres

The amyloid precursor protein (APP) family is ubiquitously expressed in the mammalian brain and implicated in Alzheimer's disease. APP family proteins participate in synaptic function and their absence impairs cognition. However, how these proteins regulate neural circuits and influence brain-behavior relationships remains …

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Differential neuronal vulnerability to C9orf72 repeat expansion driven by Xbp1-induced endoplasmic reticulum-associated degradation

Dunxin Shen, Alec Vincent, Evan Udine, Yazead Buhidma et autres

Neurodegenerative diseases are characterized by the localized loss of neurons. Why cell death is triggered only in specific neuronal populations and whether it is the response to toxic insults or the initial cellular state that determines their vulnerability is unknown. To understand …

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Human longevity and Alzheimer’s disease variants act via microglia and oligodendrocyte gene networks

Andrew Graham, Eftychia Bellou, Janet Harwood, Ümran Yaman et autres

Ageing underlies functional decline of the brain and is the primary risk factor for several neurodegenerative conditions, including Alzheimer's disease (AD). However, the molecular mechanisms that cause functional decline of the brain during ageing, and how these contribute to AD pathogenesis, are …

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Long-read transcriptomic identification of synaptic adaptation to amyloid pathology in the App NL-G-F knock-in mouse model of the earliest phase of Alzheimer’s disease

Ümran Yaman, Gareth Banks, Emil K. Gustavsson, Paige Mumford et autres

Abstract Genome-wide association studies (GWAS) have identified a transcriptional network of Alzheimer’s disease (AD) risk genes that are primarily expressed in microglia and are associated with AD pathology. However, traditional short-read sequencers have limited our ability to fully characterize how GWAS variants …

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Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease

Rikesh M. Rajani, Robert Ellingford, Mariam Hellmuth, Sam Harris et autres

Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer's disease (AD), but the underlying assumption that neurons are the main source of pathogenic Aβ is untested. Here, we challenge this prevailing belief by demonstrating that oligodendrocytes are …

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Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s Disease

Rikesh M. Rajani, Robert Ellingford, Mariam Hellmuth, Sam Harris et autres

Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer’s Disease (AD), but the underlying assumption that neurons are the main source of pathogenic Aβ is untested. Here we challenge this prevailing belief by demonstrating that oligodendrocytes are …

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THU-203 Integrated spatial transcriptomics and machine learning derived histopathology measurements in steatotic liver disease unmasks biological heterogeneity of steatosis

Carlo Sala Frigerio, Crysthiane Saveriano Rubiao Andre Ishiy, Ali Ebrahimi, Matthew Bronniman et autres

IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota

Ivo Röwekamp, Laura Maschirow, Anne Rabes, Facundo Fiocca Vernengo et autres

IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals …

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Differential neuronal vulnerability to C9orf72 repeat expansion driven by Xbp1 transcription signature

Dunxin Shen, Alec Vincent, Evan Udine, Yazead Buhidma et autres

Summary A G4C2 repeat expansion in the gene C9orf72 (C9) is the most common genetic cause of sporadic and familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). What determines why cell death is triggered only in specific neuronal populations, while others …

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Artificial intelligence for neurodegenerative experimental models

Sarah J. Marzi, Brian M. Schilder, Alexi Nott, Carlo Sala Frigerio et autres

INTRODUCTION: Experimental models are essential tools in neurodegenerative disease research. However, the translation of insights and drugs discovered in model systems has proven immensely challenging, marred by high failure rates in human clinical trials. METHODS: Here we review the application of artificial …

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Artificial intelligence for dementia genetics and omics

Conceição Bettencourt, Nathan Skene, Sara Bandrés‐Ciga, Emma L. Anderson et autres

Genetics and omics studies of Alzheimer's disease and other dementia subtypes enhance our understanding of underlying mechanisms and pathways that can be targeted. We identified key remaining challenges: First, can we enhance genetic studies to address missing heritability? Can we identify reproducible …

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