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Karin Saltoun

Doctorat - McGill
Superviseur⋅e principal⋅e
Danilo Bzdok
Sujets de recherche
Apprentissage automatique médical
Biologie computationnelle

Publications

APOE alleles are associated with sex-specific structural differences in brain regions affected in Alzheimer's disease and related dementia
Chloé Savignac
Sylvia Villeneuve
AmanPreet Badhwar
Karin Saltoun
Kimia Shafighi
Chris Zajner
Vaibhav Sharma
Sarah A. Gagliano Taliun
Sali Farhan
Judes Poirier
Danilo Bzdok
Alzheimer’s disease is marked by intracellular tau aggregates in the medial temporal lobe (MTL) and extracellular amyloid aggregates in th… (voir plus)e default network (DN). Here, we examined codependent structural variations between the MTL’s most vulnerable structure, the hippocampus (HC), and the DN at subregion resolution in individuals with Alzheimer’s disease and related dementia (ADRD). By leveraging the power of the approximately 40,000 participants of the UK Biobank cohort, we assessed impacts from the protective APOE ɛ2 and the deleterious APOE ɛ4 Alzheimer’s disease alleles on these structural relationships. We demonstrate ɛ2 and ɛ4 genotype effects on the inter-individual expression of HC-DN co-variation structural patterns at the population level. Across these HC-DN signatures, recurrent deviations in the CA1, CA2/3, molecular layer, fornix’s fimbria, and their cortical partners related to ADRD risk. Analyses of the rich phenotypic profiles in the UK Biobank cohort further revealed male-specific HC-DN associations with air pollution and female-specific associations with cardiovascular traits. We also showed that APOE ɛ2/2 interacts preferentially with HC-DN co-variation patterns in estimating social lifestyle in males and physical activity in females. Our structural, genetic, and phenotypic analyses in this large epidemiological cohort reinvigorate the often-neglected interplay between APOE ɛ2 dosage and sex and link APOE alleles to inter-individual brain structural differences indicative of ADRD familial risk.
2022-11-30
PLoS Biology (publié)
doi.org
Dissociable brain structural asymmetry patterns reveal unique phenome-wide profiles
Karin Saltoun
Ralph Adolphs
Lynn K. Paul
Vaibhav Sharma
Joern Diedrichsen
B. T. Thomas Yeo
Danilo Bzdok
2022-11-06
Nature Human Behaviour (inconnu)
doi.org
<i>APOE</i> ɛ2 vs <i>APOE</i> ɛ4 dosage shows sex-specific links to hippocampus-default network subregion co-variation
Chloé Savignac
Sylvia Villeneuve
AmanPreet Badhwar
Karin Saltoun
Kimia Shafighi
Chris Zajner
Vaibhav Sharma
Sarah A Gagliano Taliun
Sali Farhan
Judes Poirier
Danilo Bzdok
Alzheimer’s disease and related dementias (ADRD) are marked by intracellular tau aggregates in the medial-temporal lobe (MTL) and extracel… (voir plus)lular amyloid aggregates in the default network (DN). Here, we sought to clarify ADRD-related co-dependencies between the MTL’s most vulnerable structure, the hippocampus (HC), and the highly associative DN at a subregion resolution. We confronted the effects of APOE ɛ2 and ɛ4, rarely investigated together, with their impact on HC-DN co-variation regimes at the population level. In a two-pronged decomposition of structural brain scans from ∼40,000 UK Biobank participants, we located co-deviating structural patterns in HC and DN subregions as a function of ADRD family risk. Across the disclosed HC-DN signatures, recurrent deviations in the CA1, CA2/3, molecular layer, fornix’s fimbria, and their cortical partners related to ADRD risk. Phenome-wide profiling of HC-DN co- variation expressions from these population signatures revealed male-specific associations with air-pollution, and female-specific associations with cardiovascular traits. We highlighted three main factors associated with brain-APOE associations across the different gene variants: happiness, and satisfaction with friendships, and with family. We further showed that APOE ɛ2/2 interacts preferentially with HC-DN co-variation patterns in estimating social lifestyle in males and physical activity in females. Our findings reinvigorate the often-neglected interplay between APOE ɛ2 dosage and sex, which we have linked to fine-grained structural divergences indicative of ADRD susceptibility.
2022-03-14
bioRxiv (prépublication)
doi.org