Amyloid-beta buildup in mouse models of Alzheimer's changes with gene activity and human apoE types as they age

Brain Aβ42 levels were significantly lower in 9-month-old mice expressing human apoE than in age-matched control mice.

• Linear accumulation of Aβ42 began in 5-month-old apoE4 mice.
• A strong increase in Aβ42 levels was observed in 21-month-old apoE3 mice.
• Aβ42 levels in cerebroventricular fluid were higher in apoE3 than in apoE4 mice at 6-7 months of age, indicating more efficient clearance of Aβ42 by apoE3.
• ApoE3 protein levels were lower than apoE4 protein levels in the brains of 21-month-old mice, potentially explaining the rapid increase in Aβ42 burden in apoE3 mice.
• Genes identified as downregulated in an apoE-dependent and age-dependent manner may influence brain Aβ burden and Alzheimer's disease progression.

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