Journal: Cell reports

Article Title: Transcriptional signatures of hippocampal tau pathology in primary age-related tauopathy and Alzheimer’s disease

doi: 10.1016/j.celrep.2025.115422

Figure Lengend Snippet: (A) GeoMx workflow: tissue is labeled with antibodies and mRNA probes. A region of interest (ROI) is selected and then segmented by antibody labeling. A 10 μm ultraviolet light cleaves the probe barcodes, which are iteratively collected, sequenced, and analyzed from each segment. (B) Hippocampal sections stained for tau pathology (yellow, AT8) and nucleic acid (blue, SYTO13). ROIs were selected within CA1, segmented, and masked for neurons with (red, tau positive) or without (blue, tau negative) tau pathology. Transcript-specific barcodes were sequenced from each segment. (C) Higher power of positive (red) and negative (blue) neurons. (D) Principal-component analysis with PC1 accounting for 99.741% and PC2 accounting for 0.217% of the variance. (E) Differentially expressed genes in tau-positive neurons. (F) Expression of genes altered in tau-positive neurons. Significance by mixed-effects linear modeling after FDR correction. Error bars are 95% CI. AD, Alzheimer’s disease; Ctl, control; CPM, counts per million; FC, fold change; FDR, false discovery rate; Neg, tau pathology negative; Oligo, oligonucleotide; PART, primary age-related tauopathy; PC, principal component; Pos, tau pathology positive; T−, tau pathology negative; T+, tau pathology positive. Scale bars represent 50 μm. *FDR < 0.05 and **FDR < 0.01.

Article Snippet: Human hippocampal brain blocks , Johns Hopkins BRC , https://alzresearch.org/resources-for-researchers/.

Techniques: Labeling, Antibody Labeling, Staining, Expressing, Control

Journal: Genes

Article Title: Deficiency in the Ubiquitin Conjugating Enzyme UBE2A in Alzheimer’s Disease (AD) is Linked to Deficits in a Natural Circular miRNA-7 Sponge (circRNA; ciRS-7)

doi: 10.3390/genes7120116

Figure Lengend Snippet: A strong miRNA-7-UBE2A mRNA 3’-UTR interaction. ( A ) Complimentarity map of human miRNA-7 and the UBE2A mRNA 3′-UTR—an “ | ” represents a hydrogen bond between the miRNA-7 and the UBE2A mRNA 3’-UTR and “ : ” represents a partial hydrogen bond; “seed” sequences are highlighted in yellow for miRNA-7 and in red for the UBE2A mRNA 3′-UTR; an energy of association (E A ) between the miRNA-7 and the UBE2A mRNA 3′-UTR of −22.9 kcal/mol is very favorable thermodynamically; due to a deficit in ciRS-7 there are insufficient miRNA-7 sponging effects and an increase ambient miRNA-7 levels , resulting in a down-regulation in the expression of miRNA-7 targeted mRNA-3’-UTRs (such as UBE2A mRNA 3’-UTR) which is observed; other circRNAs may be involved; ( B ) levels of UBE2A protein in Brodmann area A22 and Alzheimer (ALZ) hippocampal CA1 compared to control (CON) brain postmortem samples; as in , mean and one standard deviation are shown; UBE2A is observed to be reduced to 3.6- and 2.7-fold of controls, respectively, in Brodmann A22 (the superior temporal neocortex) and the hippocampal CA1 of AD brains and the results are highly significant; insufficient UBE2A might be expected to contribute to deficits in the ubiquitination cycle that helps to clear amyloid peptides via autophagy, thus contributing to amyloidogenesis in the AD brain; in ( B ) there were no significant differences in age, ApoE allele status, RNA quality (all RIN values were 8.1–9.0) or yield between the control (CON) or Alzheimer (ALZ) groups; control UBE2A levels in the Brodmann A22 (the superior temporal neocortex) and the hippocampal CA1 of AD were arbitrarily set to 10.0; a dashed horizontal line at 10.0 is included for ease of comparison; (* p < 0.001 (ANOVA).

Article Snippet: Using a modified and highly-sensitive LED-Northern probing of AD and control brain hippocampal CA1 total RNA fractions (LED = locked nucleic acids—1-ethyl-3-3-dimethylaminopropyl carbodiimide (EDAC)—digoxigenin; LNA, EDAC, and DIG; detection limit = 0.05 fM of a single miRNA species; apparatus #170-6545, BioRad Life Science Research, Hercules, CA, USA) and a fluorescent- or radiolabeled miRNA-7 probe we detected ciRS-7 in human brain and found evidence for a significantly reduced abundance of ciRS-7 in AD to about 0.18-fold the abundance of age-matched controls ( C,D) [ , , , , ].

Techniques: Expressing, Control, Standard Deviation, Ubiquitin Proteomics, Comparison

Journal: Genes

Article Title: Deficiency in the Ubiquitin Conjugating Enzyme UBE2A in Alzheimer’s Disease (AD) is Linked to Deficits in a Natural Circular miRNA-7 Sponge (circRNA; ciRS-7)

doi: 10.3390/genes7120116

Figure Lengend Snippet: Increased miRNA-7 and deficits in ciRS-7 in AD. ( A ): up-regulated miRNA-7 in AD brain; lack of the miRNA-7 (ciRS-7) sponge by insufficient ciRS-7 suggests the miRNA-7 would be increased in the same brain regions where ciRS-7 is down-regulated as is observed; data in ( A ) quantified in bar graph format in ( B ); down-regulation of a family of miRNA-7-sensitive mRNA targets in the sporadic AD brain includes UBE2A; other mRNA targets may be involved; ( C ): detection of circRNA for miRNA-7 (ciRS-7) in sporadic AD and age-matched control hippocampal CA1 (control (CON) N = 4; AD (ALZ) N = 6]; in (C) the single upper ciRS-7 (~1400 nt) band contains ~70 selectively conserved miRNA-7 binding sites as previously described [ , , ]; a lower 28S RNA served as an internal loading and reference control; all samples depleted of rRNA were treated with 50 units of RNaseR prior to electrophoresis see [ , , ]); ( D ): AD ciRS-7 is significantly reduced to ~0.18-fold of control (CON) in AD (ALZ) hippocampal CA1 (HIPP CA1), to ~0.22 of control in the superior temporal lobe (Brodmann A22; NCTX A22) but not the brain stem (BRAINSTEM); this implicates loss of miRNA-7 sponge effects, and ambient up-regulation of miRNA-7 in at least two anatomical areas targeted by the AD process; there were no significant differences between age for control or AD tissues; (mean +/- one standard deviation (SD) = 71.6 ± 6.3 years ( N = 6; control); 73.5 ± 6.1 years ( N = 12; AD)); all AD cases were from moderate-to-advanced stages of AD; all postmortem intervals were 2.3 h or less; there were no significant differences in age, ApoE allele status, RNA quality (all RIN values were 8.1–9.0) or yield between the control or AD groups; C has been redrawn in part from ; values in (B) and (D) are normalized to control levels; a dashed horizontal line at 1.0 or 10.0 is included for ease of comparison; (* p < 0.01, ANOVA); ** p < 0.001 (ANOVA).

Article Snippet: Using a modified and highly-sensitive LED-Northern probing of AD and control brain hippocampal CA1 total RNA fractions (LED = locked nucleic acids—1-ethyl-3-3-dimethylaminopropyl carbodiimide (EDAC)—digoxigenin; LNA, EDAC, and DIG; detection limit = 0.05 fM of a single miRNA species; apparatus #170-6545, BioRad Life Science Research, Hercules, CA, USA) and a fluorescent- or radiolabeled miRNA-7 probe we detected ciRS-7 in human brain and found evidence for a significantly reduced abundance of ciRS-7 in AD to about 0.18-fold the abundance of age-matched controls ( C,D) [ , , , , ].

Techniques: Control, Binding Assay, Electrophoresis, Standard Deviation, Comparison