Possible Causes of Alzheimer’s

Alzheimer’s disease begins in the brain decades before symptoms appear. Although genetics plays a major role in the rare instances of early-onset Alzheimer’s (before the age of 65), genes have less impact on the development of late-onset Alzheimer’s disease (after the age of 65). Age itself is the major risk factor.

Today, researchers are working to understand the mechanisms of Alzheimer’s disease and to target its causes, using drug discovery to develop therapies that can slow its progression and ultimately prevent the disease. Many scientists believe that multiple causes contribute to or trigger Alzheimer’s disease and that ultimately a combination of treatments (a “drug cocktail” approach) may be most effective.

The Alzheimer's Drug Discovery Foundation (ADDF) is funding research into more than a dozen drug targets, including the six highlighted below:

Amyloid plaques are clumps of abnormal proteins that accumulate in the brains of Alzheimer’s patients and disrupt mental function. Pharmaceutical companies have made amyloid their leading drug target, investing billions of dollars into potential treatments with the aim to remove amyloid from the brains of living patients.

ApoE (apolipoproteinE) is the most significant genetic risk factor for late-onset Alzheimer’s. A certain type of ApoE – the ApoE E4 form –  increases a person’s risk of developing Alzheimer’s before the age of 75 by up to twentyfold. ADDF-funded scientists are investigating several strategies for developing drugs to modify this genetic risk.

Energy Utilization
All cells need energy to maintain healthy function, and the brain is a very high energy user. As we age, our brain cells use energy less efficiently. Decreased energy utilization is one of the earliest characteristics seen in the brains of Alzheimer’s patients. To counteract this loss, scientists are working to develop drugs that could enhance the function of the mitochondria, the energy powerhouses of cells.

Neurodegenerative diseases, including Alzheimer’s, are characterized by nerve cell death. Treatments that protect nerve cells and prevent them from dying are known as "neuroprotective" and are an important avenue for Alzheimer's researchers.

Tau is a protein in Alzheimer’s that accumulates into tangles within nerve cells in the brain, causing massive dysfunction and ultimately cell death. These tangles are a hallmark of Alzheimer’s and other related disorders. Since these tangles are so closely associated with nerve cell death, restoring the normal condition of tau protein is an important target for new drug development.

Vascular System
Damage to the body’s blood vessel network can starve the brain of oxygen and vital nutrients needed for cells to work properly. Nerve cells are particularly vulnerable. Drug development strategies that increase blood flow or promote a healthy vascular system may help to prevent the nerve cell dysfunction that is seen in Alzheimer’s.