The findings indicate a potential area of treatment for patients
Key takeaways
- Cholesterol regulation and neuronal vulnerability: The study found that neurons in the locus coeruleus (LC)a brain region highly vulnerable to Alzheimersare extremely dependent on cholesterol, both producing and absorbing it intensely. This makes them more susceptible to damage from amyloid proteins.
- Brain region comparison: By comparing two neurochemically and anatomically similar brain regions with different susceptibilities to Alzheimers, researchers identified cholesterol metabolism as a key factor in regional vulnerability. This comparison helped isolate cholesterol regulation as a potential underlying mechanism for early Alzheimers risk.
- Implications for Alzheimers treatment and prevention: Understanding the role of cholesterol in LC neuron degeneration opens new avenues for early intervention and treatment strategies.
A new study conducted by researchers at the University of California San Francisco looked at some of the neurological processes that may increase the risk of Alzheimers disease.
The researchers explained that the buildup of two proteins amyloid-beta and tau typically signal the onset of Alzheimers. The more tau builds up in the brain, the more neuron loss patients experience.
In this study, the team took a closer look at which neurons are at the greatest risk of deterioration in the earliest stages of Alzheimers. Ultimately, they learned that the brains ability to regulate cholesterol could play a key role in Alzheimers risk.
The study highlights how cholesterol regulation not only explains differences between peoples vulnerability to Alzheimers, but also differences in vulnerability between brain regions at early disease stages, senior author Dr. Lea Grinbergsaid in a news release.
The study
For the study, the researchers analyzed data from deceased patients who were enrolled in two brain banks the Neurodegenerative Disease Brain Bank at UCSF and the Biobank for Aging Studies at the University of So Paulo.
The researchers analyzed brain tissue from two different parts of the brain:
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The locus coeruleus (LC) a section of the brain that is very susceptible to Alzheimers and produces noradrenaline
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The substantia nigra (SN) a part of the brain thats resistant to Alzheimers and produces dopamine
These two regions are remarkably similar despite their markedly different vulnerabilities to Alzheimers Disease, study first author Alexander Ehrenberg, Ph.D. said.
Both are anatomically and neurochemically similar, and both are also similarly vulnerable to other neurodegenerative diseases like Parkinsons. Given this, we reasoned that the differences between the brain regions at the beginning of the study would offer clues into the baseline selective vulnerability of the LC to Alzheimers disease.
How does cholesterol play a role?
The researchers explained that the biggest difference between the two parts of the brain they studied were in cholesterol regulation.
The LC neurons exhibit signatures suggesting that they are super cholesterol-hungry these neurons are doing both their best to produce their own cholesterol and take in as much as possible, Ehrenberg said. The SN, on the other hand, doesnt have the same level of demands.
The researchers explained that because the LC neurons are producing and absorbing cholesterol so intensely, theyre more susceptible to damage from the amyloid protein. This means that theyre more likely to degenerate as Alzheimers progresses.
However, because the SN neurons can better regulate cholesterol, theyre less susceptible to Alzheimers-related proteins and arent likely to deteriorate in the same way.
A deeper understanding of the causal factors underlying LC degeneration and the development of strategies to mitigate its vulnerability could have a profound impact on the treatment of Alzheimers disease,Gringberg said.
LC dysregulation impairs critical functions such as sleep regulation and neuroinflammatory control, both of which are recognized as key risk factors that can accelerate Alzheimers progression.
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Posted: 2025-04-16 20:16:06
