Age is the major risk factor for Alzheimer’s disease. The disease begins in the brain decades before symptoms appear.

The science into the causes and mechanisms of Alzheimer's disease is ongoing, but we know that multiple factors contribute to the development of the disease. These include damaged proteins, genetics, neuronal energy failure, neuroinflammation, and vascular disease. Because of this, we believe that a combination of treatments targeting these causes may be most effective.

Alzheimer's Causes:


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.


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.


APOE (apolipoproteinE) is the most significant genetic risk factor for late-onset Alzheimer's. A certain type of APOE—the APOE4 form—increases a person's risk of developing Alzheimer's before the age of 75 by up to 20 times. ADDF-funded scientists are developing drugs to modify this genetic risk. Read more about APOE4.

Neuronal Energy Failure

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. Neuronal energy failure 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. Chronic inflammation in the brain can accelerate neurodegeneration and nerve cell death. Scientists are investigating drugs that protect against disease and injury-induced inflammation while preserving normal inflammatory responses. Read more about inflammation.

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 Alzheimers.