The brain contains billions of cells called neurons that generate and transmit electrical signals. These signals are what allow us to experience life: to think, feel, move, and remember. Alzheimer’s disease occurs when neurons in certain parts of the brain become damaged and die. As neurons die, the brain is left with less computing power, so its ability to acquire new information and recall existing memories declines. As the disease progresses and more neurons die, a person with Alzheimer’s loses their ability to understand and interact with the world around them, resulting in an inability to communicate and to complete even the simplest tasks.

Unfortunately, the reasons that these neurons die is not well understood. Researchers do know that neurons tend to die predominantly in certain regions of the brain called the cerebral cortex and the hippocampus, causing these areas to atrophy (shrink). They also know that two abnormal structural changes in the brain called plaques and tangles probably contribute to the neural death in these areas. What they don’t know is what causes these structural changes in the first place.

Another possible cause of Alzheimer’s disease symptoms is the loss of chemical messengers called neurotransmitters that are normally used to send messages between neurons. As the disease progresses, neural death causes a large decrease in the amount of a neurotransmitter called acetylcholine, which normally plays a key role in learning and memory. Reductions in brain acetylcholine levels may contribute greatly to the cognitive declines seen in Alzheimer’s patients.

Structural changes

Alzheimer’s disease was first discovered by German neurologist Alois Alzheimer in 1906. An examination of the brain of a woman with progressive dementia showed two distinct structural changes in the cerebral cortex and hippocampus: abnormal clumps of tissue outside neurons and jumbles of neural processes called axons. These two structural features, the clumps, now known as plaques, and the jumbles of axons, now called tangles, are the hallmarks of Alzheimer’s disease.

Tau and beta-amyloid proteins

While both plaques and tangles are found in the brains of everyone who dies of Alzheimer’s disease, there is much debate about which of the two is ultimately responsible for killing brain cells. Scientists don’t know whether plaques themselves cause Alzheimer’s disease or whether they are a by-product of the Alzheimer’s disease process. Similarly, researchers are unsure if tangles are directly responsible for killing neurons of if they may also be a by-product of another disease process.

Plaques are clumps of protein found in the space between neurons in the brain. Everyone who lives into old age will have some of these plaques present in their brain, but they are much more abundant in the brains of people who die of Alzheimer’s disease. These plaques are composed of a normally harmless protein called beta amyloid which is often surrounded by the fragments of dying neurons.

Some evidence suggests that these beta-amyloid plaques are the key factor that causes neurons to die in Alzheimer’s disease. In support of this theory is the fact that certain genetic mutations that result in the formation of plaques can cause early-onset Alzheimer’s disease, a rare form of the disease that strikes people between the ages of 30 and 60. Mutations in any of three proteins, the amyloid precursor protein (APP) or either of two presenilin proteins called presenilin 1 (PS1) and presenilin 2 (PS2), are responsible for most cases of early-onset Alzheimer’s. These mutations all result in early formation of amyloid plaques. Together, these three mutations cause an estimated 10% of all Alzheimer’s disease cases.

Normal, healthy neurons send messages to each other along long slender processes called axons. The structural integrity of each axon depends on a central core of long, straight proteins called microtubules that support the axon and also serve as freight railways for transporting cellular cargo. Microtubules are held in place by a protein called tau. When tau is abnormal or altered it disrupts the normal axon structure and makes cellular communication difficult. The tangles that are characteristic of Alzheimer’s disease, which are also called “neurofibrillary tangles,” are made up of axons filled with the twisted remnants of faulty tau proteins. Some researchers believe that it is the faulty tau protein and not beta-amyloid that causes neurons to become damaged and die in Alzheimer’s disease.

While everyone who dies of Alzheimer’s disease has plaques and tangles, there are certain types of plaques that can be found in the brains of people who don’t have Alzheimer’s disease. Unfortunately, it is not yet known whether people who have the plaques but no disease symptoms can live a full life and never develop the disease, or whether the plaques are an early sign of Alzheimer’s and even though they do not show symptoms of Alzheimer’s at the time the plaques are discovered, these people will eventually go on to develop the disease.