P. D. De Jager

Epigenetic mechanisms in brain development and in neurodegeneration.

Brain DNA methylation, APOE genotype and Alzheimer's disease neuropathology in a large postmortem cohort.

DNA methylation (DNAm) plays a critical role in Alzheimer's disease (AD). Previous epigenome-wide association studies using 450K arrays captured limited CpG coverage and often focused on a single neuropathological measure. Here we profiled DNAm in 1,250 postmortem prefrontal cortex samples from the Rush Alzheimer's Dis...

Fibronectin mediates APOE4-driven blood–brain barrier dysfunction in Alzheimer’s disease

Blood–brain barrier (BBB) dysfunction is an early feature of Alzheimer’s disease (AD) and is particularly pronounced in individuals carrying the APOE ε4 allele, but the mechanisms linking APOE ε4 to BBB failure remain unclear. Here we show that astrocyte-derived fibronectin (FN1) is a key mediator of apolipoprotein E4...

HIGH-DIMENSIONAL MULTI-OMIC MAPPING OF POST-MORTEM HUMAN BRAIN USING ITERATIVE INDIRECT IMMUNOFLUORESCENCE IMAGING ON XENIUM-PROCESSED TISSUES

A post-spatial profiling workflow that combines the Xenium platform with iterative indirect immunofluorescence imaging (4i) on formalin-fixed paraffin-embedded (FFPE) human brain tissue to capture key pathological features for Alzheimer’s disease (AD) and facilitate cell segmentation is reported.

Evaluation of potential serum biomarkers for individuals at risk of multiple sclerosis highlights SPP1.

Investigating whether alterations in six previously MS-associated biomarkers are detectable and associated with underlying genetic susceptibility in two independent sample collections suggest that several circulating proteins recently proposed as MS biomarkers are not robust tools to distinguish MS from healthy individ...

Genome-wide association analyses highlight the neuronal contribution to multiple sclerosis susceptibility

Inhibitory neurons emerged as a key target cell type for MS-associated variants, with seven loci, including STAT3, displaying altered expression only in these cells, suggesting that MS susceptibility may reflect reduced central nervous system resilience to inflammatory challenges.

Altered microglial communication in brains with Alzheimer’s Disease pathology

It was found that AD was characterized by altered microglial composition and rewiring of intercellular communication, including disease-specific signaling pathways and distinct interaction hubs.