Why Don’t We Have a Treatment for Alzheimer’s?

a doctor's prescription pad
Dr. Sharon Orrange
Dr. Orrange is an Associate Professor of Clinical Medicine in the Division of Geriatric, Hospitalist and General Internal Medicine at the Keck School of Medicine of USC.
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Alzheimer’s disease (AD) accounts for 70% of dementia. The brain affected by Alzheimer’s has two things normal brains don’t. The first is a build-up of protein fragments, called amyloid plaques, between nerve cells in the brain. The second is the tangling of a protein, tau, in nerve cells. Confusing, I know, but it’s why we don’t have a good treatment for Alzheimer’s.

At present, only two types of medications are currently used to attempt to halt the progression of the disease: cholinesterase inhibitors like Aricept, Exelon, Razadyne and NMDA receptor antagonists like memantine (Namenda) which help with minor improvement in memory and cognition. They aren’t great.

For 20 years, the simplified explanation for Alzheimer’s has been this: in normal subjects, the protein amyloid is degraded, but in a brain with Alzheimer’s, the ability to remove amyloid is decreased causing it to accumulate in the brain. An increase in the level of amyloid causes nerve cell death and degeneration. But, is this explanation accurate?

Is this why treatments are failing?

Recent advances in brain imaging have made us wonder if amyloid deposits in the brain are a regular phenomenon of aging, which may have no direct relation with the onset of Alzheimer’s. Here’s why – in some cases, in the brain of elderly non-demented patients, the distribution of plaques is sometimes as extensive as that of dementia patients. So amyloid may not be affecting Alzheimer’s.

In the past few years, various treatments, like immunotherapies, have failed to show benefit. This unexpected failure of all trials of Alzheimer’s treatment drugs targeting amyloid may be explained if the main factor causing progression of Alzheimer’s is in fact the protein tau, not amyloid. Back to the drawing board.

Let’s hope…

Dr O.

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