Biology subjects

Abdourahman, A.

Publications and source records attributed to Abdourahman, A..

2 recordsLinked to original sources

bioRxiv2023

Distinct Transcriptomic Responses to A beta plaques, Neurofibrillary Tangles, and APOE in Alzheimer's Disease

INTRODUCTIONOmics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimers disease (AD) but the spatial relationships with plaques and tangles and APOE-linked differences remain unclear. METHODSWe performed laser capture microdissection of A{beta} plaques, the 50m halo around them, tangles with the 50m halo around them, and areas distant (>50m) from plaques and tangles in the temporal cortex of AD and control donors, followed by RNA-sequencing. RESULTSA{beta} plaques exhibited upregulated microglial (neuroinflammation/phagocytosis) and downregulated neuronal (neurotransmission/energy metabolism) genes, whereas tangles had mostly downregulated neuronal genes. A{beta} plaques had more differentially expressed genes than tangles. We identified a gradient A{beta} plaque>peri-plaque>tangle>distant for these changes. AD APOE{varepsilon}4 homozygotes had greater changes than APOE{varepsilon}3 across locations, especially within A{beta} plaques. DISCUSSIONTranscriptomic changes in AD consist primarily of neuroinflammation and neuronal dysfunction, are spatially associated mainly with A{beta} plaques, and are exacerbated by the APOE{varepsilon}4 allele.

neuroscience↗

bioRxiv2022

Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer's disease

Astrocytes play a critical role in brain homeostasis and normal functions but their changes along the spatiotemporal progression of Alzheimers disease (AD) neuropathology remain largely unknown. Here we performed single-nucleus RNA-sequencing on brain regions along the stereotypical progression of AD pathology from donors ranging the entire normal aging-AD continuum comprising 628,943 astrocyte nuclei from 32 donors across 5 brain regions. We discovered temporal gene-expression-trajectories with gene sets differentially activated at various disease stages. Surprisingly, a gene set enriched in proteostasis and energy metabolism, was upregulated in late-stage but unexpectedly returned to baseline levels in end-stage, suggesting exhaustion of response in "burnt-out" astrocytes. The spatial gene-expression-trajectories revealed that astrocytic genes of tripartite synapses are dysregulated in parallel to the stereotypical progression of tangle pathology across regions. We identified astrocyte heterogeneity across brain regions with a continuum from homeostatic to reactive cells through "intermediate" transitional states. These findings suggest complex astrocytic dysfunction in AD neurodegeneration.

neuroscience↗