This research was done in a mouse model and may or may not be applicable to humans.
From the article [emphasis mine]:
Open access paper: https://www.pnas.org/content/118/33/e2102191118The scientists then did a series of experiments in aged "3xTg-AD" mice, which are genetically engineered to overproduce Aβ, to develop Aβ plaques, and broadly to model Alzheimer's. They found that when they shut off astrocyte cholesterol production in the mice, Aβ production plummeted to near-normal, and Aβ plaques virtually disappeared. Another classic Alzheimer's sign usually seen in these mice is the accumulation of tangled aggregates of a neuronal protein called tau—and those disappeared too.
...
"You couldn't just eliminate cholesterol in neurons, cholesterol is needed to set a proper threshold for both Aβ production and normal cognition," Hansen says.
The findings offer new evidence of the underlying factors advancing development of Alzheimer's. A common variant of the apoE gene, known as the E4 variant, is the largest risk factor for late-onset Alzheimer's, and Hansen and colleagues found evidence in the study that this variant, compared to the more common, lower-risk E3 variant, somehow boosts APP's association with lipid rafts, which thus boosts Aβ production.
Hansen and his laboratory are currently studying how apoE's transport of cholesterol and maintenance of lipid rafts in the brain impacts not only Aβ production but also brain inflammation—another feature of Alzheimer's that contributes to destruction in the brain but has murky causes.
"There is the suggestion here of a central mechanism, involving cholesterol, that could help explain why both Aβ plaques and inflammation are so prominent in the Alzheimer's brain," Hansen says.
Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol
Hao Wang, Joshua A. Kulas, Chao Wang,David M. Holtzman, Heather A. Ferris, and Scott B. Hansen
PNAS August 17, 2021 118 (33) e2102191118;
DOI: 10.1073/pnas.2102191118
You may want to jump directly to the discussion section to start with a mix of readability and technical details before reading the rest of the paper.
