Controlling cholesterol levels has been linked to preventing neurodegenerative diseases, including Alzheimer’s and Parkinson’s.
A recent study published in Experimental and Molecular Medicine highlights the potential role of regulating cholesterol in reducing the risk of neurodegenerative conditions. Also, the Lancet Commission identified high low-density lipoprotein (LDL) cholesterol levels after age 40 as one of 14 modifiable risk factors for dementia. The commission outlined four molecular mechanisms by which cholesterol imbalance may contribute to neurodegeneration.
First, synaptic function, essential for nerve cell communication, depends on plasma membrane cholesterol. A shortage of cholesterol can impair synaptic transmission, leading to cognitive and motor function decline—hallmarks of neurodegenerative diseases.
Second, cholesterol is crucial for cell membrane structure and protein clustering. Insufficient cholesterol in nerve cells can cause membrane defects, potentially triggering neurodegeneration.
Third, cholesterol imbalance affects the aggregation and modification of proteins like amyloid precursor (APP). Elevated cholesterol levels can enhance beta-amyloid production from APP, forming beta-amyloid plaques characteristic of Alzheimer’s disease.
Finally, cholesterol influences the formation of Lewy bodies and alpha-synuclein accumulation, key factors in Parkinson’s disease.
The study also notes that cholesterol cannot directly cross the blood-brain barrier (BBB); most brain cholesterol is produced locally. However, the interaction between peripheral cholesterol in the bloodstream and brain cholesterol can impact neurodegeneration.
Elevated blood cholesterol levels can contribute to atherosclerotic plaques in blood vessels, including those supplying the brain, reducing the oxygen and nutrients delivered to brain tissue and accelerating neurodegeneration.
Moreover, high blood cholesterol levels can compromise the BBB’s integrity. Damage to the BBB may allow peripheral molecules that typically can’t enter the brain to pass through, potentially causing neuroinflammation and further neurodegeneration.
The researchers and the Lancet Commission suggest that issues with cholesterol synthesis in the brain or disruptions in cholesterol regulation within nerve cells underlie these mechanisms. To protect brain health, they recommend lowering LDL levels and increasing high-density lipoprotein (HDL) levels through lifestyle changes such as quitting smoking, managing blood pressure, maintaining a healthy diet, and engaging in regular physical and social activities.
The Centers for Disease Control and Prevention (CDC) provides guidelines for lowering LDL cholesterol, including maintaining a healthy weight, exercising regularly, quitting smoking, moderating alcohol intake, reducing saturated and trans fats, salt, and added sugars, and increasing fiber and unsaturated fats.
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