Alzheimer's brain vs. normal brain: What to know

What happens to the brain in Alzheimer’s?

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Over time, a brain with Alzheimer’s shrinks. Neurons die, and plaques accumulate in areas such as the hippocampus. The brain may change for up to a decade or longer, prior to symptoms of Alzheimer’s manifesting.

Alzheimer’s disease usually begins in the hippocampus, which is the part of the brain that plays a role in memory and thinking.

Typical brains metabolize (process) a chemical called amyloid precursor protein (APP). In Alzheimer’s, APP turns into a protein called beta-amyloid, which the brain does not clear away.

Instead, the proteins form clumps and tangles that stick between and damage the neurons. The clumps of beta-amyloid protein can also destroy connections between the neurons, causing them to die.

People with Alzheimer’s also often have abnormal tangles of a protein called tau. This protein usually resides inside neurons in people with healthy brains. But in Alzheimer’s, beta-amyloid interacts with tau proteins to cause abnormal clumps and tangles of the protein. This creates plaques in the brain, which are areas of reduced neurons and brain death.

Beta-amyloid and tau

Researchers are still working to fully understand how tau and beta-amyloid interact, as well as why some people’s brains respond abnormally to these proteins.

A 2020 study found that the presence and location of tau protein in the brain may predict future brain damage and help with predicting the course of Alzheimer’s. Drawing on brain scans of 32 people with Alzheimer’s disease, researchers concluded that tau might play a more direct role in brain damage than beta-amyloid.

Additionally, people with Alzheimer’s tend to have inflammation in their brains. Inflammation accumulates in the brain as people age, but it is more severe in dementia.

Some research suggests that this happens because the brain becomes less able to clear waste. In healthy brains, cells called microglia destroy toxins. The brains of people with Alzheimer’s do not do this as well.

A gene called TREM2 instructs microglia to get rid of beta-amyloid plaques in healthy brains, reducing inflammation. But abnormal functioning of this gene can reduce the action of microglia, leading to plaques and inflammation.

While research continues to look at the role of beta-amyloid and tau, researchers have also found plaques and tangles in the brains of people who do not have Alzheimer’s. Moreover, some people with symptoms of dementia do not have these changes in their brains.

This suggests that a complex interaction of many factors is the cause of dementia, and that it may not always be possible, especially in the early stages, to distinguish an Alzheimer’s brain from a healthy brain.

Blood flow

In some cases, changes in the blood vessels of the brain and in blood flow to the brain may increase the risk of dementia. People with blood vessel blockages in the brain are more likely to develop dementia.

Changes in blood flow to the brain can further damage the brain, making it even more likely that the brain will struggle to clear toxins, which can lead to harmful effects. This means that Alzheimer’s may cause vascular changes in the brain, and also that it may happen because of these changes.

Other types of dementia

Alzheimer’s is not the only type of dementia. Other types of dementia affect the brain in slightly different ways.

For example, fronto-temporal dementia affects the frontal or temporal lobes of the brain. This initially affects behavior, speech, or both. As the disease progresses, it may look more like Alzheimer’s, causing memory loss and other forms of brain dysfunction.

To differentiate Alzheimer’s from other dementias, a doctor may look at a combination of symptoms and brain changes.

Learn more about Alzheimer’s here.

Differences in function 

Alzheimer’s fundamentally changes how the brain works. In the popular imagination, it primarily affects memory. But this is just in the early stages. As it moves through the cerebral cortex, it can affect virtually every aspect of functioning, ultimately causing the brain to fail.

In the early stages, some differences in brain function may include:

• memory problems that begin as short-term memory difficulties and progress to more serious issues, such as not remembering a loved one
• word-finding difficulties
• frequently losing things
• wandering
• getting lost

Learn more about the early signs of Alzheimer’s and other types of dementia here.

In the middle stages of the disease, some manifestations of brain changes may include:

• sleep difficulties, such as not being able to sleep or wandering at night
• confusion about time and place
• becoming withdrawn or apathetic
• incontinence of the bladder and bowels
• personality changes that may cause suspiciousness, anger, or depression
• delusions and hallucinations

As Alzheimer’s progresses further, it begins to affect other areas of functioning, including the brain’s ability to coordinate the body’s functions. Some symptoms may include:

• not being able to engage in self-care such as bathing and getting dressed
• needing help with eating
• problems with physical functions such as walking
• swallowing issues
• organ failure
• frequent infection, such as pneumonia
• death

Alzheimer’s proceeds in relatively predictable stages based on how the brain damage progresses. A person in late stage Alzheimer’s will always have great difficulty with basic functions. But the speed at which a person progresses and the specific symptoms that are most noticeable in each stage varies from person to person.

Summary

Understanding the differences between the brains of people with and without Alzheimer’s may eventually help researchers discover a cure. Current treatments aim to slow Alzheimer’s-related brain changes, such as by slowing the damage to the brain, or helping nerve cells better communicate with one another.

But these treatments do not cure or reverse Alzheimer’s.

One of the challenges of understanding Alzheimer’s and the brain is that it is not easy to see the brain, and doctors cannot view all changes until after a person has died.

Additionally, researchers continue to find that there is no clear factor that differentiates a person with Alzheimer’s from one without the disease, since some people have plaques and tangles without symptoms, and others have symptoms without brain changes.

Alzheimer’s is a complex disease, and many questions about how it works in the brain remain.