Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model

Jan 26, 2020The Journal of neuroscience : the official journal of the Society for Neuroscience

Removing Trem2 lowers late amyloid plaque buildup, increases harmful amyloid ratio, and worsens nerve fiber and spine damage in an Alzheimer's mouse model

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Abstract

PS2APP; mice showed impaired microgliosis and increased neuritic dystrophy despite reduced amyloid plaque accumulation at later ages.

  • Microglia in PS2APP;Trem2 mice had compromised expression of genes related to cell proliferation and marked accumulation of ApoE.
  • Plaque abundance was elevated in PS2APP;Trem2 females at 6-7 months but decreased in both sexes by 12-22 months.
  • Plaque morphology was more diffuse in PS2APP;Trem2 brains, with an elevated Aβ42:Aβ40 ratio and increased soluble, fibrillar Aβ oligomers.
  • Axonal dystrophy worsened from 6 to 7 months in PS2APP;Trem2 mice, indicating a strong relationship with microglial deficiency rather than amyloid plaque load.
  • Increased dendritic spine loss and neurofilament light chain in cerebrospinal fluid were observed in PS2APP;Trem2 mice, suggesting neuronal vulnerability.

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Key numbers

12 of 24 months
Decrease in Plaque Load
Reduced plaque accumulation observed in PS2APP; mice at older ages.
7 months
Increase in Axonal Dystrophy
Axonal dystrophy exacerbated from 7 months onward in PS2APP; mice.
2.3×
Elevated Aβ42:Aβ40 Ratio
Aβ42:Aβ40 ratio higher in PS2APP; brains across ages.

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