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Ms4a4a deficiency ameliorates plaque pathology in a mouse model of amyloid accumulation
Lack of Ms4a4a reduces plaque buildup in mice with amyloid accumulation
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Abstract
Ms4a4a deficiency reduced steady-state (Aβ) levels and shortened its half-life in brain interstitial fluid.
- Aged 5xFAD mice lacking Ms4a4a exhibited more compact plaques and lower overall plaque burden.
- Microglia deficient in Ms4a4a showed a pro-inflammatory profile and elevated production of (MMP-9).
- Increased levels of cerebrospinal fluid MMP-9 were observed in human carriers of the AD-resilient variant rs1582763 near MS4A4A.
- The findings suggest that loss of MS4A4A enhances Aβ clearance and reduces Alzheimer's disease pathology.
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Key numbers
0.87 hours
Decrease in Aβ half-life
Aβ half-life in 5xFAD 4A-KO mice
2.7×
Increase in MMP-9 levels
MMP-9 levels in RAB-soluble fraction of 5xFAD 4A-KO mice
0.02
Reduction in plaque burden
Plaque burden quantification in the hippocampus of 5xFAD 4A-KO mice