What Alzheimer’s does to the brain?

What Alzheimer’s does to the brain?

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About 50 million people worldwide live with Alzheimer’s disease. And with aging populations in many countries, the numbers suffering from this disease are steadily increasing. We know that Alzheimer’s is caused by problems in the brain. The cells begin to lose function and eventually die, leading to memory loss, cognitive decline, and even major changes in personality. Separate areas of the brain are also narrowed in process of atrophy, which leads to significant loss of brain volume. But what exactly is happening in the brain leads to this?

The main route of spread of the disease is through disruption of communication between neurons, special cells that process and transmit electrical and chemical communication between brain regions. It leads to death of brain cells and, as we think, to the accumulation of two types of proteins, amyloid and Tau. The exact interaction between these two proteins is largely unknown, but amyloid accumulates in sticky clusters, known as beta amyloid “plaques”, as Tau accumulates inside dying cells, known as “neurofibrillary tangles”.

One of the difficulties of diagnosis of Alzheimer’s disease is that we have no reliable and accurate method to measure these protein accumulations in the early stages of the disease. In fact, we are unable to definitively diagnose Alzheimer’s disease up until the patient doesn’t die, exploring the actual brain tissue.

Another problem is that beta amyloid plaques can also be found in the brain of healthy patients. This suggests that the presence of amyloid and Tau proteins can not explain the entire history of this disease.

More recent studies show that there is a role to play in chronic inflammation. Inflammation is a part of the body’s defense system against disease, which occurs when white blood cells release chemicals to protect the body from foreign substances. But over a sufficiently long period of time it can cause damage.

In the brain, damaging tissue long-term inflammation may be caused by the accumulation of cells known as microglia. In a healthy brain, these cells absorb and destroy waste and toxins. But in patients with Alzheimer microglia cannot clear this debris, including toxic Tau tangles or amyloid plaques. The body activates more microglia in an attempt to clear this debris, which in turn leads to inflammation. Long-term or chronic inflammation gradually damages brain cells and ultimately leads to their death.

Recently, scientists have identified a gene called TREM2, which may be responsible for this problem. Usually TREM2 directs microglia for purification of beta-amyloid plaques in the brain and helps to fight inflammation in the brain. But the scientists found that the brains of patients, the gene TREM2 which is not working correctly, accumulate beta-amyloid plaques between neurons.

Many Alzheimer’s patients also have problems with the heart and circulatory system. Beta-amyloid deposits in brain arteries, atherosclerosis (hardening of the arteries) and mini-strokes may also play a role.

Vascular problems can further reduce blood flow in the brain and destroy the blood-brain barrier, a structure that is important for removal of toxic waste from the brain. This can also prevent the brain to absorb all the necessary glucose — some studies have suggested that this may occur before the appearance of toxic proteins associated with Alzheimer’s disease in the brain.

Scientists deeper into the brain, in particular in the precise connections between neurons, known as synapses. A recent study published in Nature, describes a process in cells, which may contribute to the destruction of these synaptic connections between neurons. The data show that it may occur when there is not enough of a particular synaptic protein (also known as RBFOX1).

Through this kind of research, currently, there are many new drugs that are being tested and developed with the aim to resolve one or more changes in the brain that occur in Alzheimer’s disease. Many researchers believe that a more personalized approach to patients with Alzheimer’s disease is the future.