Journal: bioRxiv

Article Title: Therapeutic targeting of fibrin–microglia interactions ameliorates Alzheimer’s disease-related hyperexcitability and brain network dysfunction

doi: 10.64898/2026.05.01.722324

Figure Lengend Snippet: Brain tissue from human AD (A) and from 5xFAD, App SAA/SAA , App NLG/NLG , and App NLG/NLG :APOE4 mice (B-D) were stained for fibrin(ogen) (red), Aβ (blue), and the microglia marker Iba1 (green) primary antibodies (scale bar, 25 mm). ( A ) In AD brain tissue, fibrin(ogen) deposition was found within amyloid plaques (#), diffusely around some of the blood vessels (*), and decorating blood vessels (arrowheads). Representative images are shown from n = 3 samples. ( B ) 10-month-old 5xFAD mice showed robust fibrin(ogen) deposition within and around amyloid plaques and decorating blood vessels (arrowheads). Reactive microglia (green) accumulated around amyloid and fibrin(ogen) deposits. Representative images are shown from n = 10 samples. ( C, D ) Relative to 5xFAD mice (B), 21-month-old App NLG/NLG (C) and 15-month-old App NLG/NLG :APOE4 (D) mice showed more diffuse fibrin(ogen) deposition around amyloid plaques, with fibrin(ogen) forming an external halo around amyloid plaques. Reactive microglia cells (green) accumulated around amyloid and fibrin(ogen) deposits. Representative images are shown from n = 6–10 samples per genotype.

Article Snippet: App SAA mice were obtained from The Jackson Laboratory (Jax 034711).

Techniques: Staining, Marker

Journal: bioRxiv

Article Title: Circadian disruption induces sex-specific Alzheimer’s pathophysiology and immune cell reprogramming

doi: 10.64898/2026.04.30.721994

Figure Lengend Snippet: (A) A schematic representing the workflow of the TMT analysis of BMDMs. (B) The total number of circadian proteins (harmonic/damped/forced) in each of the categories, represented in a bar chart. Dark blue/black outline = male littermate (LM), light blue/black outline = male APP/PS1 (AP) mice, red/black outline = male circadianly disrupted (CD), orange/black outline = male CD/AP, dark blue = female littermate (LM), light blue = female AP, red = female CD, orange = female CD/AP. (C) Radial histograms of the number of oscillating proteins that reach their peak phase at a given circadian timepoint (CT). (D) Heatmaps of proteins with significant circadian oscillations. Scaled expression values (-1 to +1) are shown for post-serum-shock and CT time points. Proteins are ordered along the y-axis by peak phase timing. (E) UpSet plot displaying the number of proteins that are rhythmic across each group, separated by males and females. Fill color indicates genotype/lighting condition for C-E (dark blue = LM, light blue = AP, red = CD, orange = CD/AP). ♂ = male, ♀ = female. See also Figures S3 and S4 and Tables S4 and S5.

Article Snippet: Hemizygous APPswe/PS1dE9 (APP/PS1) mice and non-transgenic littermate controls were obtained from Jackson Laboratory.

Techniques: Expressing

Journal: bioRxiv

Article Title: Circadian disruption induces sex-specific Alzheimer’s pathophysiology and immune cell reprogramming

doi: 10.64898/2026.04.30.721994

Figure Lengend Snippet: A diagrammatic summary of the effects of CD on macrophage circadian function and early AD-related pathology. Standard lighting conditions are depicted by a normal clock (top left), while the CD condition is represented by a distorted clock with misaligned hands (top right). Pictorial representations of male (♂; top row; solid lines) and female (♀; bottom row; dashed lines) APP/PS1 (AP) mouse macrophages, brains, and circadian proteomic oscillations are shown under standard and disrupted lighting conditions (CD/AP). Macrophages and brains appear pink when naïve and red/darker with increased inflammation states. The black dashed arrow indicates peripheral macrophage trafficking toward the brain. Brown tangles represent relative amyloid-β plaque burden. Representative circadian oscillations illustrate average phase relationships and CD-induced phase shifts. Arrows above the oscillations denote the direction and relative magnitude of phase change under CD/AP conditions compared with AP alone. The width of the shaded traces represents the alignment of the phases of the proteins within immunometabolic pathways. “Immunometabolic phase alignment” indicates increased temporal alignment of immunometabolic pathways in female CD/AP macrophages.

Article Snippet: Hemizygous APPswe/PS1dE9 (APP/PS1) mice and non-transgenic littermate controls were obtained from Jackson Laboratory.

Techniques: