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Alzheimer's disease (AD) is the most common, irreversible and progressive form of dementia. The World Alzheimer's Disease 2018 Report shows that every 3 seconds, 1 person with dementia is born worldwide.
Currently, there are at least 50 million people with dementia worldwide, and it is expected that by 2050, 152 million, of which about 60%-70% will be Alzheimer's disease (AD) patients.
Alzheimer's disease in the late 20th century was widely known as the "long goodbye" due to the slow deterioration of brain function and memory. However, more than 100 years ago, scientist Alois Alzheimer first discovered plaques in the brains of patients with the disease. Since then, one of the hallmarks of Alzheimer's disease (AD) has been the accumulation of amyloid β plaques in the brain.
Although the deposition of amyloid-β (A-β) in the brain is one of the pathological features of Alzheimer's disease, it has been linked to neurodegeneration in both human patients and animal models of the disease. But A-β is also present in peripheral organs, and A-β levels in the blood are associated with amyloid burden and cognitive decline in the brain.
Does amyloid-β produced in other organs cause Alzheimer's disease?
Recently, a new study published in the open journal PLOS Biology found that β amyloid produced in the liver is carried in the blood through lipoproteins to the brain, causing neurodegeneration in the brain. This suggests that the liver may play an important role in the onset or progression of Alzheimer's disease.
https://doi.org/10.1371/journal.pbio.3001388
In the study, to distinguish between A-β produced by brains and peripheral organs, the researchers developed a mouse that produced only human A-β in liver cells.
Experiments have shown that in mice, A-β produced by the liver are able to enter the brain through the bloodstream through lipoproteins rich in triglycerides. The accumulation of A-β in the brain caused the experimental mice to develop neurodegeneration and brain atrophy, accompanied by neurovascular inflammation and cerebral capillary dysfunction, which are common markers of Alzheimer's disease.
Aβ produced in the liver contributes to pathological changes in the brain associated with alzheimer's disease
In addition, the affected mice performed poorly on a learning test that depended on the function of the hippocampus, an important brain structure for forming new memories.
The results of this study suggest that peripherally derived A-β have the ability to cause neurodegeneration and suggest that A-β produced in the liver are a potential contributor to human disease. If this contribution is enormous, then these findings could have a major impact on understanding Alzheimer's disease.
As mentioned earlier, A-β produced by the liver are able to enter the brain through the bloodstream through triglyceride-rich lipoproteins. This also shows that lipoproteins (the core component is triglycerides, surrounded by a layer of phospholipids, cholesterol, protein molecules) also play a role in Alzheimer's disease.
For lipoproteins, a previous study found that high levels of low-density lipoprotein cholesterol (LDL-C) in middle age were associated with an increased risk of developing dementia ten years later. The findings showed that among people under the age of 65 who measured cholesterol, people with LDL-C levels above 190 mg/dL had about a 60 percent higher risk of being diagnosed with dementia more than 10 years later compared to people with levels below 100 mg/dL.
DOI:10.1016/S2666-7568(21)00150-1
To date, most models of the disease have focused on overproduction of A-β in the brain, which mimics rare genetic cases of Alzheimer's disease in humans. But for the vast majority of AD cases, overproduction of A-β in the brain is not considered to be at the heart of the disease's cause. Instead, lifestyle factors may play a more important role, including a high-fat diet, which may accelerate the liver's production of A-β.
Aerobic exercise, healthy eating, non-smoking, and restricted alcohol consumption are known to be the most important lifestyle factors for maintaining liver, blood-brain barrier, and brain health. Therefore, adopting this healthy lifestyle may keep liver, cardiovascular, and brain function sharper for a longer period of time.
Mamo added. "While further research is needed now, this finding suggests that the large deposition of A-β in the blood may be addressed through an individual's diet and some drugs that specifically target lipoprotein amyloid, thereby reducing the risk of Alzheimer's disease or slowing the progression of Alzheimer's disease."
Both dementia and Alzheimer's disease are devastating diseases for individuals and their loved ones, and so far, there is no cure, so active prevention remains key. Protecting your memory and mind starts with maintaining the right levels of LDL!
bibliography:
1.Synthesis of human amyloid restricted to liver results in an Alzheimer disease–like neurodegenerative phenotype. PLOS Biology, 2021; 19 (9): e3001358 DOI: 10.1371/journal.pbio.3001358
2.Blood cholesterol and risk of dementia in more than 1·8 million people over two decades: a retrospective cohort study