Diet gun

The crucial effects of cholesterol in the brain on different cellular processes in the central nervous system have become apparent in recent decades.

The brain contains ≈ 25% of the total amount of cholesterol in the body.

Due to the blood-brain barrier, the central nervous system does not absorb cholesterol from the bloodstream and relies exclusively on its own endogenous synthesis.

Developmental Period of Cholesterol in the Brain

The largest percentage of cholesterol in the brain is synthesized and accumulated intensively during human development, that is, from the perinatal period to adolescence.

Myelin and Cholesterol

Myelin is the protective sheath around nerves, which is largely composed of cholesterol. Myelin speeds up signals between nerves, protects nerves by preventing leaks so that the nerve signal reaches its destination intact, and supports movement and thought as its action is vital for reflexes, balance, coordination of movements, and cognitive functions.

Adult Life, Brain Cholesterol, and Myelin

After myelosis is complete in adolescence, most of the brain’s cholesterol becomes a stable pool with an extremely slow rate of renewal and minimal losses in adulthood.

That is, the brain maintains a delicate balance of cholesterol levels through a precisely regulated process.

This process is governed by the coordinated efforts of neurons, astrocytes, and oligodendrocytes and is essentially protected by the blood-brain barrier.

Disruption of this balance, as demonstrated by various studies, serves as a key trigger for neurodegenerative diseases, such as AD (Alzheimer’s disease), PD (Parkinson’s disease), and HD (Huntington’s disease).

As we age, the formation and distribution of cholesterol is disrupted for the following reasons:

1. Astrocyte and neuron deficiency

The cells that synthesize and recycle cholesterol in the brain malfunction, reducing the efficiency with which they distribute it to neurons.
2. Synapse destruction

Proper lipid organization is essential for the proper transmission of brain signals. If cholesterol is not in the right place or amount in the cell membrane, communication is disrupted.

3. Accumulation of Oxidized Products (Oxysterols)

In normal aging, cholesterol byproducts (such as 27-hydroxycholesterol) accumulate and can cross the blood-brain barrier, causing inflammation and degeneration.

4. Genetic Factors

The presence of certain transport proteins (such as APOE4) prevents the proper transport of cholesterol between brain cells.

5. Myelin Degradation

As myelin (the protective sheath of nerves) deteriorates over time, the cholesterol that is released is not properly reused, leading to toxicity.

As we mentioned above, brain cholesterol becomes a fixed pool with an extremely slow renewal rate after adulthood. Anything that can negatively affect, more than normal, one or more of the factors that renew brain cholesterol can quickly create neurological diseases such as Alzheimer’s Disease, Parkinson’s Disease or Huntington’s Disease.

Statins/Simvastatin and Blocking Remyelination

Cholesterol is a key structural component of myelin.

Because statins reduce cholesterol synthesis, several studies show that they can inhibit the maturation of myelin-producing cells (oligodendrocytes), delaying healing in damaged areas.

Also in experimental models of demyelination (e.g., multiple sclerosis), we have seen that long-term administration of potent lipophilic statins (such as simvastatin) can inhibit the maturation of progenitor cells into mature oligodendrocytes. This interferes with myelin repair and, in prolonged exposure, can cause the cell extensions to regress, that is, myelin repair is inhibited, resulting in its reduction, disrupting the balance and causing neurological diseases.

Neurodegenerative diseases are a type of irreversible neurological disorders caused by the gradual loss or even death of neuronal structure or function in the brain and spinal cord.

The effects of lipid-lowering therapies raise thoughts and questions.

While statins and PCSK9 inhibitors are effective in managing hypercholesterolemia, their effects on brain cholesterol and cognitive health require further investigation as so far they show that they disrupt balances that should not be disturbed.

Why have neurodegenerative diseases increased since the 1990s?

Yes, life expectancy has increased in many countries, but is it coincidental that statins have become widely available since 1987?

Today, more than 200 million people worldwide take statins, with the most popular being atorvastatin, simvastatin, and rosuvastatin, which account for 70% of total use.

Manipulations of cholesterol within the CNS that bypass the blood-brain barrier through genetic, pharmacological, or metabolic measures have produced a range of mixed results.
Cholesterol is associated with cognitive function in old age, although the association is strongly age-dependent. However, there is no evidence to prove that statin treatment in the elderly has a beneficial effect on cognitive function; rather, the opposite is true.


Sources and articles that may help:
Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases
Brain Cholesterol Metabolism and Its Defects: Linkage to Neurodegenerative Diseases and Synaptic Dysfunction
Cholesterol imbalance and neurotransmission defects in neurodegeneration
Genetic connections between neurological disorders and cholesterol metabolism
Brain cholesterol homeostasis and its association with neurodegenerative diseases
Negative Impact of Statins on Oligodendrocytes and Myelin Formation In Vitro and In Vivo
Statin Therapy Inhibits Remyelination in the Central Nervous System
Cholesterol: Its Regulation and Role in Central Nervous System Disorders
Outcome age-based prediction of successful cognitive aging by total cholesterol
Cholesterol Metabolism in the Brain and Its Association with Parkinson’s Disease
Higher levels of ‘good’ cholesterol may help preserve brain health
The Effects of Cholesterol on Learning and Memory
Cholesterol and late-life cognitive decline
Cholesterol imbalance and neurotransmission defects in neurodegeneration
Cholesterol and the risk of dementia
Thwarting Alzheimer’s Disease through Healthy Lifestyle Habits: Hope for the Future