Mind Thief by Yu Han

Author:Yu, Han
Language: eng
Format: epub
Tags: SCI034000, Science/History, HEA039140, Health & Fitness/Diseases/Alzheimer's & Dementia
Publisher: Columbia University Press
Published: 2021-02-03T00:00:00+00:00

Except for some early-phase trials that recruit healthy participants (who can better tolerate any unknown side effects of experimental drugs), Alzheimer’s drug trials typically recruit mild or mild-to-moderate Alzheimer’s patients to test the drugs’ cognitive effects. Yet these typical patients, Baptists say, may be too far along to be saved. Their brains have accumulated so much beta-amyloid, which has caused too much damage that no amount of antiamyloiding would save them.

An analogy here is cholesterol-lowering drugs. These drugs reduce cholesterol and prevent heart disease. However, if cholesterol has already built up in the arteries, blocked blood flow, and caused a heart attack, cholesterol-lowering drugs—no matter how effective at lowering cholesterol—won’t save us. By the same token, antiamyloid drugs—no matter how effective at lowering ­beta-amyloid—won’t help us if we are already suffering from cognitive decline.

The analogy sounds reasonable—compelling even. Being compelling, it has ushered in a new way of thinking about beta-amyloid that resembles a paradigm shift.

In the old days, we thought that beta-amyloid was the driver of Alzheimer’s.17 In this hypothesis, beta-amyloid accumulates in the brain, driving cognitive function to go downhill gradually. By reducing beta-amyloid, we can hope to slow, or even reverse, cognitive symptoms. But according to autopsies and brain imaging studies, beta-amyloid is not exclusive to old age. It begins building up in the brain in our forties (or twenties even),18 decades before possible dementia symptoms—just as cholesterol silently builds up in the arteries. It is only when buildup reaches a certain threshold that symptoms start to show.19

Given this fact, drugs fail if they don’t reduce beta-amyloid to levels below the threshold. Even if they did, there’s no guarantee of success because once beta-amyloid goes beyond the threshold, it might trigger events and damage that take on lives of their own: tau protein continues to build up, neurons continue to die, and brain function continues to fade.

So, in order for a drug to work, the safest bet is to take it before beta-amyloid hits that threshold. Baptists don’t know where the threshold is, other than that it happens well before cognitive symptoms appear. Mild and mild-to-moderate patients have obvious symptoms ranging from memory lapses to confusion to difficulty with daily living activities. Given this fact, the amount of beta-­amyloid deposits in their brains must have gone well beyond the threshold; ergo, it’s already too late.

Future trials, Baptists urge, must recruit people who are in danger, but not yet showing symptoms. The goal should be to prevent Alzheimer’s for them, not to treat Alzheimer’s.

But how do we find people who need saving when they are still symptom free? One sure way is through the early-onset Alzheimer’s communities: the Volga Germans, Colombian Paisas, and others. Using genetic testing, we can identify people from these communities who carry mutations that destine them for Alzheimer’s. If a drug can delay or even prevent their fate, then we have a winner.

This is the method used by the Alzheimer’s Prevention Initiative, an international research consortium, and its sponsor, Genentech, a San Francisco–based biotech subsidiary of the Swiss pharmaceutical company Roche.

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