Die meisten Alzheimer-Fälle würden ohne den Beitrag nur dieses einzigen Gens nicht auftreten: Apoe. Wenn Interventionen die schädlichen Auswirkungen beseitigen könnten [of Apoe3 and 4]können wir damit rechnen, die Alzheimer-Krankheit (72-93 %) und einen großen Teil aller Demenzerkrankungen (45 %) zu verhindern.

Alzheimer’s therapies should target a particular gene, researchers say

New therapies for Alzheimer’s disease should target a particular gene linked to the condition, according to researchers who said most cases would never arise if its harmful effects were neutralised.

In searching for alternative therapies, scientists at UCL say drug developers should focus on two risk-raising variants of a gene named Apoe. Therapies designed to block the variants’ impact have “vast potential” for preventing the disease, they claim.

Dr Dylan Williams, a genetic epidemiologist at UCL, said: “**Most Alzheimer’s disease cases would not arise without the contribution of just this single gene: Apoe.** We need to think about it as a direct target. Almost all potential Alzheimer’s cases could benefit from Apoe-related interventions.”

Williams and his colleagues analysed medical records from more than 450,000 people of European ancestry to calculate how much Alzheimer’s disease arose due to different variants of the Apoe gene. People inherit two copies of the gene – one from each parent – and there are three main variants: Apoe2, 3 and 4.

Scientists have long known that people with two copies of Apoe4 are high risk for Alzheimer’s, though 40% to 70% never develop the disease. The Apoe3 variant is widely considered neutral and the rare Apoe2 variant is regarded as protective.

But Williams said we should see it another way. Compared with carrying two copies of Apoe2, both Apoe3 and Apoe4 raise the risk of Alzheimer’s, he said. Writing in the journal npj Dementia, the team calculate that without these variants, 72% to 93% of Alzheimer’s cases, and about 45% of all dementia, would not have occurred. “**If interventions could eliminate the detrimental effects [of Apoe3 and 4], we could expect to prevent most Alzheimer’s disease and a large proportion of all dementia**,” they write.

For those interested, here’s the link to the peer reviewed journal article:

https://www.nature.com/articles/s44400-025-00045-9

This paper is flat-out wrong.

There are two hallmark symptoms in Alzheimer’s: „plaques“ and „tangles“. Of those two, the evidence clearly shows the tangles are the real culprit.

There was a paper back in 2008 that implicated the plaques, but it ended up being retracted when it turned out the data was faked.

I have sympathy for plaque researchers. It sucks finding out you’ve been looking in the wrong place for 15 years on account of fake data. But continuing to do plaque research as if the entire field wasn’t built on a lie is just silly.

Sigh, this was a shoddy article. We know that the E4 gene is a risk allele and E2 is protective. The question becomes how does that translate to disease biology? There is good evidence that APOE is acting to a degree through increasing amyloid deposition, but there are also additive effects on tau. There are drugs in the works targeting those two proteins with the approved drugs in the US being anti-amyloid. APOE also is show to impact these AD core pathologies through inflammatory processes, so maybe drugs should target inflammation. Maybe you would even design drugs to target APOE itself. Literally all of this is already in play. This article didn’t tell me anything that virtually every scientist in the field already knows.

There were also two things that particularly annoyed me.

„Scientists have long known that people with two copies of Apoe4 are high risk for Alzheimer’s, though 40% to 70% never develop the disease.“ So this is just patently false. Almost everyone with two copies of the APOE E4 allele have high levels of the pathology in the brain. They may die from other causes before they get dementia, but they definitely have the disease. This is dangerous thinking as written as people with pathology, but without overt dementia, are likely the best group to target. Think giving statins to people prior to heart attacks as a parallel. This is likely where most drug approaches are going to end up.

„Compared with carrying two copies of Apoe2, both Apoe3 and Apoe4 raise the risk of Alzheimer’s, he said. Writing in the journal [npj Dementia](https://doi.org/10.1038/s44400-025-00045-9), the team calculate that without these variants, 72% to 93% of Alzheimer’s cases, and about 45% of all dementia, would not have occurred.“ This is an absolutely idiotic statement. E2 isn’t the common variant. It is very rare, and considered protective. E3 is the default. They even acknowledge this later on, saying that 99% of the world isn’t a E2E2 carrier.