Studies show that cholesterol plays a crucial role in brain health.

You've certainly heard that there's good cholesterol (HDL) and bad cholesterol (non-HDL or LDL). But did you know that one of the places in the body where this dichotomy is most evident is in the brain? Recent studies reveal the role of cholesterol in both maintaining the organ's health and accelerating its decline. And the composition of the fat has everything to do with these different effects.

For a long time, cholesterol's role in the brain was seen only as a villain, especially due to its association with strokes in the organ. However, over the last decade, studies have shown that the brain depends on it to function properly. The organ is composed of about 60% fat and needs lipids to maintain the structure of nerve cells and the transmission of electrical signals. This, however, does not mean just any fat.

“It’s a complex division and depends on the quality of that cholesterol,” explains neurologist Marco Túlio Pedatella, coordinator of Neurology at the Einstein Israelite Hospital in Goiânia. “It’s not just about thinking in terms of general levels; even the proportion of proteins associated with HDL cholesterol has an impact on the effects it will have on the brain.”

The balance, therefore, is delicate. While good fats are essential for the formation and maintenance of neuronal functions, from another perspective, an excess of lipids, especially LDL types that accumulate in the form of droplets in the organ, is linked to inflammation and cognitive decline.

When cholesterol protects or harms

Several studies have been conducted to understand the impacts of this distinct role of cholesterol in the brain. One of them, carried out by researchers at the University of Texas in the United States and published in the Journal of Clinical Medicine in October 2024, revealed that HDL may even have a neuroprotective effect.

Imaging studies conducted on 1,800 adults showed that those with higher HDL levels had, on average, a greater volume of gray matter in the brain, which may be associated with better preservation of cognition with aging. This beneficial association held even in patients who had the ApoE4 gene, linked to Alzheimer's disease.

Another study, published in the journal Immunity in July 2025, focused on "bad" cholesterol, LDL. The research revealed that having high levels of this type of fat between the ages of 40 and 65 significantly increases the risk of Alzheimer's and other forms of dementia in the following decades. According to research by neuroscientists at Purdue University, also in the USA, excess fat can paralyze microglia, the brain's defense cells.

They discovered that a lipid enzyme, DGAT2, accumulates in these cells and reduces their ability to eliminate amyloid plaques, protein buildups highly associated with Alzheimer's disease. The study also found, in vitro , that by eliminating the fat enzymes, the cellular function of these brain "cleaners" fully recovered.

“These findings reinforce the importance of maintaining a balanced lipid metabolism to preserve brain health throughout life,” emphasizes cardiologist Fabiana Hanna Rached, an atherosclerosis specialist at Einstein Hospital Israelita. “Imbalanced cholesterol in the brain affects communication between neurons, impairs synaptic function, and can contribute to cognitive decline.”

The good news is that keeping cholesterol under control — especially LDL — can reduce the risk of cognitive decline. Studies indicate that the use of statins and dietary changes help not only to protect the heart, but also to slow down or even prevent dementia.

Cholesterol that only affects the brain.

Although the body produces cholesterol in various tissues, brain cholesterol is "particular." It is synthesized there and does not freely cross the blood-brain barrier, which isolates the nervous system, so its levels may differ from the rest of the body. "Brain cholesterol has its own metabolism, and only derivatives such as 24S-hydroxycholesterol can cross this barrier," explains Pedatella. This separation helps protect the nervous system from abrupt variations in circulating fat.

Despite this, systemic body disorders associated with lipid levels, such as metabolic syndrome, can indirectly affect brain cholesterol metabolism. Individuals with abdominal obesity, hypertension, and low HDL levels in the blood, for example, often have reduced brain volume. “Although healthy fats are crucial for cognitive function and brain health, having low HDL levels associated with other metabolic problems has even been linked to lower cognitive performance in tests, so we need to investigate further whether reversing or improving metabolic syndrome can benefit brain health and in what ways,” notes Rached.

Furthermore, the stage of life when cholesterol levels rise seems to determine the future risk of dementia. "The impact of cholesterol levels on the risk of dementia is most significant when exposure occurs in middle age," warns the neurologist. After age 70, this association weakens, and higher levels may even be linked to a better prognosis in some studies.

These contradictions indicate that there is still much to understand. “Longitudinal studies capable of distinguishing cause and effect of cholesterol in the brain are lacking. It is also necessary to investigate how early interventions, such as balanced diets and metabolic control, can preserve brain function,” emphasizes the cardiologist from Einstein.

Meanwhile, it's worth following this maxim: managing cholesterol through a good diet, medication when necessary, and physical activity isn't just a matter of heart health; it's also an investment in overall health, including brain health.

Source: Einstein Agency

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