THE PATHOPHYSIOLOGY OF ALZHEIMER’S DISEASE

The aggregation and accumulation of different forms of amyloid beta is a key pathological feature of Alzheimer’s disease (AD).1

An imbalance between production and clearance

Research has shown that when amyloid beta is no longer properly cleared from the brain, it accumulates and may lead to neurodegeneration long before the first symptoms of AD become visible.1-6

This understanding of AD highlights the importance of early detection and diagnosis as a central component of future patient care.

Understanding the Pathophysiology of Alzheimer’s Disease

Transcript

Speaker 1 (00:05):

Many people, as they get older, may notice changes in memory and thinking abilities. At first, these changes may be so subtle that they're easy to explain away as normal aging, and they may be. However, it's also possible that they're the earlier symptoms of Alzheimer's disease. Alzheimer's disease, or AD, is the most common form of dementia and accounts for 60% to 80% of all cases of dementia. In the United States alone, it is thought that one person develops AD every 66 seconds on average. In the early stages, people with AD may notice everyday tasks becoming more difficult to perform than before. Some typical early symptoms of AD you may notice include facing increased problems with memory, struggling to find the right words for things, becoming confused about time or place, having trouble managing money or paying bills, experiencing changes in mood, personality, or judgment, misplacing or being unable to find things.

Speaker 1 (1:13):

The symptoms of AD arise because of slow, ongoing injury to different parts of the brain. This injury, which affects nerve cells, is believed to be the result of two different processes that occur in the brains of people with AD. One involves a protein called amyloid beta, or A-beta, and the other involves a protein named tau. In the first of these processes, A-beta starts to collect inside the brain. This may begin as many as 20 years before the first signs of AD appear. A-beta is produced inside the brains of all people, but in healthy people, it is removed by the body before it can cause harm. In the brains of people with AD, A-beta clumps together in bigger and bigger groups and forms clusters known as plaques

Speaker 1 (02:05):

As time goes on, plaques begin to form in more and more parts of the brain, which are responsible for learning, memory and other tasks. The second process, involving tau protein, begins about 15 years before the first signs of AD appear. Tau normally plays a helpful role in the brain. However, in people with AD, tau becomes altered and forms tangles within nerve cells. Eventually, the processes involving A-beta and tau can injure nerve cells. As this injury affects one brain region after another, it leads to the appearance of symptoms you may recognize. AD is a disease that progresses over time, leading to worsening symptoms, and can ultimately cause death.

Amyloid beta and the start of AD

It is believed that Alzheimer’s disease is based on the buildup of two proteins in the brain—amyloid beta and tau—thought to be caused by advanced age and/or genetic factors.1,7-9

One of the pathological hallmarks of Alzheimer’s disease is amyloid beta accumulation, due to an imbalance in production and inadequate clearance in the brain.1,7-9

Multiple Forms of Amyloid Beta Result From Abnormal Accumulation and Aggregation in the Brain10

Hover over descriptors to see categories of amyloid beta.

Soluble

Insoluble

Aggregated

Monomer

Oligomer

Fibril

Amyloid plaque

Amyloid beta monomers (single peptides) aggregate into soluble oligomers (small aggregates of peptides), which then combine to form insoluble fibrils (long aggregates of peptides) and plaques.1

Amyloid beta oligomers are soluble and may spread throughout the brain. Fibrils are larger aggregrates that are insoluble and assemble into amyloid beta plaques.10

It is unclear whether all or only some of these amyloid beta forms are damaging to the brain, but there is evidence to support that aggregated forms, such as oligomers and plaques, may be toxic to nerve cells.¹

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