Link between metabolic disorders and Alzheimer's disease
- owenhaskins
- Feb 20
- 3 min read
Research led by Professor Yanping Sun and Professor Lan Tan from Qingdao University, Qingdao, Shandong, China, have reported how disrupted fat metabolism might contribute to the development and progression of Alzheimer's disease (AD).
Research in recent years has yielded a growing body of evidence linking AD to metabolic syndrome (MetS), a cluster of simultaneously-occurring conditions which includes diabetes, obesity, high blood pressure and abnormal blood fat levels or dyslipidaemia.
While research has established some connections between AD and these individual conditions, the precise relationship between AD and each component of MetS remains unclear, particularly regarding the underlying biological mechanisms.
"The brain is largely composed of lipids, which are crucial for maintaining the structure and function of neurons," explained Sun. "By knowing the connections between MetS and AD, and the specific mechanisms by which dyslipidaemia contributes to AD, it will be possible to identify new treatment targets and potentially develop therapeutic strategies in the future."
The comprehensive literature review reveals intricate connections between diabetes and AD, suggesting that issues related to insulin regulation might contribute to AD's development in unexpected ways.
When the body becomes insulin resistant, it produces more of the hormone to maintain normal blood sugar levels. However, excess insulin can interfere with the brain's ability to clear away Aβ proteins, potentially leading to the formation of harmful amyloid plaques, a hallmark of AD. This connection is so significant that some researchers have begun referring to AD as "type 3 diabetes."
High blood pressure, another key component of MetS, appears to have its own distinct impact on brain health. Existing research suggests that midlife hypertension may significantly increase the risk of developing dementia later in life.
Brain imaging studies have also shown that high blood pressure can reduce the thickness of the brain's cortex and potentially promote the development of AD, particularly in individuals carrying specific genetic risk factors like apolipoprotein E4 (APOE4).
The relationship between obesity and AD presents a complex picture, with timing apparently playing a crucial role. Research indicates that being overweight in the middle years, rather than in later life, may be more strongly linked to the development of different forms of dementia and cognitive decline. Brain scans of obese individuals have revealed changes similar to those seen in AD, including reductions in gray matter volume.
Perhaps most intriguingly, the review highlights how dyslipidaemia may play a central role in connecting these various conditions to AD. Various past analyses have found links between dysregulation in the metabolism of cholesterol and fatty acids with harmful brain or neuronal conditions. These include neuronal inflammation, Aβ protein buildup, blood-brain barrier breakdown, and oxidative stress, which were all analysed in detail from a molecular biology perspective in the article.
Importantly, this literature review points to the fact that maintaining healthy blood fat levels may be more important for brain health than previously thought. Promising preventive or therapeutic strategies that are currently under study even include cholesterol-lowering medications and dietary approaches, such as Mediterranean and ketogenic diets and omega-3 fatty acid supplementation.
"Approximately one-third of Alzheimer's cases worldwide may be linked to modifiable risk factors," noted Sun, "With the increasing prevalence of high-fat diets and longer lifespans, understanding how MetS and dyslipidaemia contribute to cognitive decline has become critical."
Overall, this comprehensive review represents a step towards cementing our current understanding of the complex relationship between lipid metabolism and brain function. Even as the occurrence of both MetS and AD continues to rise globally, these insights could play a vital role in the development of more effective prevention strategies and treatments.
The findings were featured in the paper, ‘Association between Alzheimer's disease and metabolic syndrome: Unveiling the role of dyslipidemia mechanisms’, published in the Brain Network Disorders. To access this paper, please click here
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