If amyloid buildup is part of normal aging, what causes Alzheimer’s disease?

If amyloid buildup is part of normal aging, what causes Alzheimer’s disease?

  • The formation of amyloid plaques in the brain is currently the dominant theory of what causes Alzheimer’s disease.
  • Researchers from the USC Leonard Davis School have found that even healthy brains have higher levels of amyloid protein as the brain naturally ages, and it’s not always a sign of Alzheimer’s disease.
  • Instead, the problem may be that some brains are unable to clear enough of the accumulated amyloid protein.
  • The research team says their findings support the use of PET imaging to check the brain for increased amyloid protein and the development of drugs to directly target the cellular mechanisms that eliminate beta-amyloid.

Although scientists still don’t know exactly what causes a type of dementia called Alzheimer’s disease, the prevailing theory continues to focus on the formation of amyloid plaques in the brain.

Now researchers at the USC Leonard Davis School have found evidence suggesting higher levels of amyloid protein in the brain occurs naturally with aging and is not always a sign of Alzheimer’s disease.

The researchers showed that the soluble form of beta-amyloid was not correlated with the brain mechanisms of Alzheimer’s disease. However, the fibrillar form of beta-amyloid – which forms potentially disruptive plaques – was associated with disease progression.

That’s why the study authors believe the problem may lie in the reduced ability of some brains to eliminate some of this protein as it accumulates.

The study has just been published in Alzheimer’s and dementiathe journal of the Alzheimer’s Association.

What are amyloid plaques?

Amyloid precursor protein (APP) is a protein in the body that helps with various cellular functions. This protein plays an important role in helping neurons in the brain grow and repair themselves.

APP can be broken down via two ways – one that helps break down protein, and another that leads to buildup of beta-amyloid.

Recent work has shown that soluble beta-amyloid may play a beneficial role in neuronal cell and synapse function. However, excess soluble beta-amyloid can be toxic to the brain.

Due to its molecular structure, beta-amyloid is known to be “sticky”, which means that it can sometimes clump together with other proteins, forming amyloid plaques that deposit on the outside of neurons.

These amyloid plaques can impair neuronal function but are less harmful to neuronal function than the soluble form. Some researchers believe that their formation is a protective mechanism to prevent the impact of excess soluble beta-amyloid.

Amyloid protein in the aging brain

For this study, the researchers looked at postmortem brain tissue samples from people with healthy brains and others with dementia aged 66 to 99 at the time of death.

After analysis, scientists found similar amounts of soluble substances, non-fibrillar amyloid protein — which can be toxic and associated with the development of Alzheimer’s disease — in both populations.

“We were surprised to find a large overlap between cognitively normal patients and Alzheimer’s patients for the soluble or non-aggregated form of amyloid proteins,” said Dr. Max Thorwald, postdoctoral researcher at USC Leonard Davis School. and first author of this study. Medical News Today.

“We also found that the precursor to this protein was reduced in the brains of people with Alzheimer’s disease compared to cognitively normal brains. [brains]” he added.

Evidence for or against the existing theory?

Additionally, researchers have found higher levels of beta-amyloid in the brain tissue of people with Alzheimer’s disease. So if increased levels of amyloid don’t explain the disease, what does?

“Aggregated forms of these peptides increased in Alzheimer’s brains as expected,” Dr. Thorwald told us. “We hypothesize that reduced clearance of amyloid protein also contributes to Alzheimer’s disease. »

“These results further support the use of aggregated or fibrillar amyloid as a biomarker for treatments of Alzheimer’s disease,” he added. “The site where amyloid processing occurs has fewer precursors and enzymes available for processing, which may suggest that amyloid clearance is a key issue in Alzheimer’s disease. »

The research team believe their findings support the use of positron emission tomography (PET) imaging of other people, whether or not they have symptoms of Alzheimer’s disease, to check the presence of an increase in amyloid protein.

” [And] these results suggest that new drugs for amyloid protein clearance could be developed to treat Alzheimer’s disease,” said Dr. Thorwald.

Adding to what we know

DTM also spoke with Dr. Heather Snyder, vice president of medical and scientific relations for the Alzheimer’s Association, about this study.

She noted that these findings add to Previous search who found similar levels of beta-amyloid production in the brains of healthy individuals and people with cognitive impairment, but that clearance rates – the ability to remove waste products from the brain – were more impaired in people with Alzheimer’s disease.

“This study further adds to the idea that targeting compensatory mechanisms in the brain may impact not just beta-amyloid, but the mechanisms themselves,” Dr. Snyder said. “There are preliminary studies underway based on the idea of ​​stimulating and correcting clearance mechanisms as potential strategies for the treatment of Alzheimer’s disease. »

“The Alzheimer’s Association’s Part the Cloud program is funding the work of Dr. Lyndon Lien of Qinotto, Inc., who is conducting a Phase 1 study of a drug that activates lysosomesthat contribute to degrading and eliminating waste from a cell, for the treatment of neurodegeneration,” she added.

Tips for treating Alzheimer’s disease

DTM also spoke with Dr. David A. Merrill, psychiatrist and director of the Pacific Brain Health Center of the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California, about this study.

“It is interesting to read that soluble amyloid increases with normal aging, implying that amyloid may play some role in normal brain function with aging, which is different from the idea that amyloid is the enemy and its mere presence means you have Alzheimer’s disease.

– Dr. David A. Merrill

Dr Merrill said the study implies that Alzheimer’s disease is the result of a problem with amyloid removal, leading to plaque buildup.

“The implication is that treatments aimed at assisting the clearance of amyloid may be useful in preventing the progression of Alzheimer’s disease,” he continued. “My understanding is that this is in line with new drugs recently approved that would help reduce the amyloid plaque load in the brain. »

“What the field needs are safe treatments [and] that do not lead to significant amounts of brain swelling and brain bleeding,” Dr. Merrill added.

“And then, ideally, we would also see treatments that not only reduce the amounts of amyloid deposits, but also improve brain structure and function, such as improving neuronal function, improving memory, instead to simply slow down the progress. [However,] it is better to slow the progression than to have no treatment,” Dr. Merrill said.

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