Possible Causes of Alzheimer’s

Alzheimer’s disease begins in the brain decades before the 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 drugs that can slow and ultimately prevent it. Many scientists believe that multiple causes may contribute to or trigger Alzheimer’s disease and ultimately a combination of treatments, or “drug cocktail” approach may be most effective.

The following is a list of six drug targets that the ADDF has targeted.

“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 20-fold. ADDF-funded scientists are investigating several strategies for developing drugs to modify this genetic risk.

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 – known as the energy powerhouse of the cell.

Neurodegenerative diseases such as Alzheimer’s are characterized by nerve cell death. Treatment strategies to guard nerve cells and prevent them from dying are referred to as “neuroprotection.”

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 as well as 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.

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. Therefore, drug development strategies that increase blood flow or promote a healthy vascular system may prevent the nerve cell dysfunction that is seen in Alzheimer’s.