Knockout of apolipoprotein A‐I decreases parenchymal and vascular β‐amyloid pathology in the Tg2576 mouse model of Alzheimer's disease

Deletion of the APOA1 gene significantly reduced concentrations of insoluble Aβ40 and Aβ42 in Tg2576 mice.

• ApoA-I knockout mice showed reduced plaque load in both brain tissue and blood vessels compared to Tg2576 mice.
• The decrease in Aβ levels was not linked to changes in Aβ production or variations in Aβ species.
• Soluble clusterin/apoJ levels were significantly higher in neurons of apoA-I knockout mice than in wildtype and apoA-I KO × Tg2576 mice.
• Increased clearance of Aβ was observed along drainage pathways in apoA-I knockout mice compared to wildtype animals.
• These findings indicate that the absence of apoA-I may enhance Aβ clearance and lower Aβ pathology in the context of Alzheimer's disease.

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