Distinct Transcriptomic Responses to A beta plaques, Neurofibrillary Tangles, and APOE in Alzheimer's Disease
Das, S.; Li, Z.; Wachter, A.; Alla, S.; Noori, A.; Abdourahman, A.; Tamm, J. A.; Woodbury, M.; Talanian, R. V.; Biber, K.; Karran, E. H.; Hyman, B. T.; Serrano-Pozo, A.
Show abstract
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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Rare genetic variation in Fibronectin 1 (FN1) protects against APOEe4 in Alzheimer's disease 98%
- Low circulating choline, a modifiable dietary factor, is associated with the pathological progression and metabolome dysfunction in Alzheimers disease. 97%
- Genome-wide association study and functional validation implicates JADE1 in tauopathy 96%
Similar papers in this journal
- Deciphering cellular transcriptional alterations in Alzheimer's disease brains 97%
- Interrogating the plasma proteome of repetitive head impact exposure and chronic traumatic encephalopathy 96%
- Characterization of mitochondrial DNA quantity and quality in the human aged and Alzheimer’s disease brain 96%
Similar papers in this journal
- A public resource of single cell transcriptomes and multiscale networks from persons with and without Alzheimer's disease 98%
- Identification of Chlamydia pneumoniae and NLRP3 inflammasome activation in Alzheimer's disease retina 97%
- DNA methylation signatures of Alzheimer's disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types 97%
Similar papers in this journal
- Spatially resolved transcriptomics reveals unique gene signatures associated with human temporal cortical architecture and Alzheimer's pathology 98%
- Emergence of distinct and heterogeneous strains of amyloid beta as Alzheimer s disease progresses in Down syndrome 97%
- Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction, progression, and prion-like spread of Alzheimer s disease pathogenesis 96%