• Modeling Mechanism：

  PLX5622 selectively inhibits the colony-stimulating factor 1 receptor (CSF1R) signaling pathway, leading to the survival-dependent loss of microglia (intrinsic myeloid cells in the brain), achieving long-term, specific depletion (brain clearance rate > 95%). After microglia depletion, Aβ cannot form dense plaques in the brain parenchyma and instead deposits in cerebral blood vessels (mimicking cerebral amyloid angiopathy, CAA), while reversing the disordered expression of AD-related neuronal genes, revealing the key role of microglia in AD plaque formation.

• Related Products：

  PLX5622 (T7100)

• Modeling Method：

  Experimental Subject：

  Mice, 5xFAD (AD transgenic model), Wild-type (WT), 1.5 months old

  Dosage and Administration Route：

  ① Core intervention: PLX5622 hemifumarate, 1200 ppm, mixed into AIN-76A standard chow, ad libitum feeding;
  ② Control treatment: Standard AIN-76A diet, Ad libitum feeding;
  ③ Administration period: Initiation at 1.5 months of age, continuing through weeks 10–24 (covering the critical AD plaque formation phase), with endpoint assessment at 4–7 months of age;
  ④ Recovery validation (optional): Discontinue PLX5622 feed after 10 weeks of administration, revert to standard feed for 1 month, observe microglial recovery and plaque reformation

  Dosing Frequency and Duration Model：

  Core period: 10 weeks or 24 weeks, ad libitum feeding
  Reversal validation: "10 weeks of dosing+1 month of withdrawal"

• Validation：

  Pathological markers: Microglia depletion: Immunohistochemistry (IBA1 staining) showed a 97%-100% reduction in the number of microglia in the cortex and hippocampus, with only a small number of cells remaining in the thalamus and submental region; Plaque formation: The number of dense plaques in the brain parenchyma (Thio-S staining) decreased by 60%-90%, and significant cerebral vascular Aβ deposition (CAA) was observed in the cortex; a small number of plaques could still form around surviving microglia; Molecular markers: The total amount of Aβ₁₋₃₈, Aβ₁₋₄₀, and Aβ₁₋₄₂ in the brain remained unchanged, but the deposition location shifted from the brain parenchyma to blood vessels; the downregulation of hippocampal neuronal synapse-related genes (such as Dync1l1 and Gls) was reversed; Behavioral markers: Morris water maze and elevated cross maze showed that microglia depletion did not affect the cognitive function of mice and improved anxiety-like behavior in 5xFAD mice; Rejuvenation verification: Microglia were rejuvenated after PLX5622 was discontinued, brain parenchymal plaques reformed, and their number returned to the level of untreated 5xFAD mice.

*Precautions： At the end of the treatment, the mice were euthanized by inhaling CO2 and carefully perfused with 1X phosphate-buffered saline (PBS).

*References：Spangenberg E,et,al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model. Nat Commun. 2019 Aug 21;10(1):3758.