Elena E. Galea, Spain
Universitat Autònoma de Barcelona Institut de NeurociènciesAuthor Of 1 Presentation
THE PHENOTYPIC TRANSFORMATION OF ASTROCYTES IN ALZHEIMER’S DISEASE UNRAVELED BY THE BIOINFORMATIC COMPARTMENTALIZATION OF CORTICAL TRANSCRIPTOMES FROM PATIENTS INTO CELL-SPECIFIC GENE CLUSTERS
Abstract
Aims
The lack of astrocyte-specific transcriptomics from patients with Alzheimer’s disease (AD) hinders our understanding of the impact of astrocytes in AD. Here, we sought to identify changes in astrocytes using whole-brain transcriptomes from human patients and bioinformatic tools.
Methods
An astrocytic gene cluster was generated from a RNAseq database of healthy human brain cells (Zhang et al., Neuron, 2016. 89(1): p. 37-53) using a cell-type enrichment score and hierarchical clustering. The astrocyte cluster was co-localized in whole-brain transcriptomes from 766 subjects with mild cognitive impairment (MCI), AD or controls obtained from three databases (MtSINAI, Mayo Clinic and ROSMAP). Comparison of astrocytic genes among cohorts was performed by gene set and principal component analyses.
Results
All cohorts were molecularly heterogeneous, suggesting coexistence of disease types or stages within each cohort. Astrocytes in MCI and AD showed downregulation of ‘mitochondria’ and ‘endomembrane system’, and upregulation of ‘stress responses’, ‘plasticity’, and ‘perisynaptic astrocyte processes’/’gliotransmission’.
Conclusions
Astrocytes undergo a profound transcriptional change in MCI and AD, affecting organelles, particularly the endolysosomal system and mitochondria, as well as astrocyte-neuron interactions. The analysis suggests that therapies preventing organelle dysfunction in astrocytes may protect neural circuits in AD.
Presenter of 2 Presentations
THE PHENOTYPIC TRANSFORMATION OF ASTROCYTES IN ALZHEIMER’S DISEASE UNRAVELED BY THE BIOINFORMATIC COMPARTMENTALIZATION OF CORTICAL TRANSCRIPTOMES FROM PATIENTS INTO CELL-SPECIFIC GENE CLUSTERS
Abstract
Aims
The lack of astrocyte-specific transcriptomics from patients with Alzheimer’s disease (AD) hinders our understanding of the impact of astrocytes in AD. Here, we sought to identify changes in astrocytes using whole-brain transcriptomes from human patients and bioinformatic tools.
Methods
An astrocytic gene cluster was generated from a RNAseq database of healthy human brain cells (Zhang et al., Neuron, 2016. 89(1): p. 37-53) using a cell-type enrichment score and hierarchical clustering. The astrocyte cluster was co-localized in whole-brain transcriptomes from 766 subjects with mild cognitive impairment (MCI), AD or controls obtained from three databases (MtSINAI, Mayo Clinic and ROSMAP). Comparison of astrocytic genes among cohorts was performed by gene set and principal component analyses.
Results
All cohorts were molecularly heterogeneous, suggesting coexistence of disease types or stages within each cohort. Astrocytes in MCI and AD showed downregulation of ‘mitochondria’ and ‘endomembrane system’, and upregulation of ‘stress responses’, ‘plasticity’, and ‘perisynaptic astrocyte processes’/’gliotransmission’.
Conclusions
Astrocytes undergo a profound transcriptional change in MCI and AD, affecting organelles, particularly the endolysosomal system and mitochondria, as well as astrocyte-neuron interactions. The analysis suggests that therapies preventing organelle dysfunction in astrocytes may protect neural circuits in AD.
LIVE DISCUSSION
- Dan Frenkel, Israel
- Howard Weiner, United States of America
- Boyd Kenkhuis, Netherlands
- Pablo Largo-Barrientos, Belgium
- Ilse Dewachter, Belgium
- Philip J. De Jager, United States of America
- Melinda Barkhuizen, Switzerland
- Mariko F. Taga, United States of America
- Elena E. Galea, Spain
- Afroditi A. Tsitsou-Kampeli, Israel
