Fluctuating Cholesterol Levels And Alzheimer Risk: The ApoE Link

Too much cholesterol and heart disease risk is a well-established connection. However, a lesser-known link would be that between cholesterol levels and ApoE Alzheimer’s risk. Intrigued yet? Turns out, the same genes implicated in Alzheimer’s also have a role to play in cholesterol clearance from the body. A new study has revealed surprising insights into how fluctuating cholesterol levels can increase Alzheimer’s risk.

Did You Know? ApoE gene comes in 3 forms, E2, E3, and E4, each of which affects cholesterol metabolism. One particular form is associated with poor cholesterol removal and a resultant increased risk for heart disease. Watch this video to learn more:

Alzheimer’s: A Brief Overview

Alzheimer’s is a common type of dementia affecting 5.8 million American adults.

This condition is characterized by memory loss, poor judgment, inability to participate in a conversation, and mood and behavioral changes.

As the condition progresses, it can lead to complete memory loss and the inability to speak, walk, or even swallow.

Beyond 65, the risk of developing the condition doubles every five years.

Currently, Alzheimer’s disease doesn’t have a cure. It can only be managed with medications and intervention strategies.

Role Of Cholesterol In The Body

Cholesterol is a waxy, fat-like substance produced by the liver and found in many food sources.

Cholesterol is an integral component of cell membranes to maintain their fluidity and integrity.

The body also needs cholesterol to make vitamin D, bile acid, and steroid hormones.

Dangers Of High Cholesterol Level

Excess cholesterol in the blood can combine with other substances and form plaque.

Plaques are deposits that stick to the inner walls of blood vessels and cause blocks.

Plaque buildup is a common cause of coronary artery disease.

High cholesterol levels are also associated with increased risk of peripheral artery diseases, hypertension, stroke, and high blood pressure.

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How Does Cholesterol Metabolism Affect the Brain?

The Central Nervous System (CNS) stores up to 25% of the cholesterol levels in the body.

Cholesterol levels play a role in the physiological functioning of the brain.

According to experts, very little dietary cholesterol enters the brain because of the Blood Brain Barrier.

The brain cells synthesize most of the cholesterol that the brain needs internally.

Does The Brain Need Cholesterol?

The brain needs cholesterol for the following functions.

Synapse formation (points of contact between neurons for transfer of information)
Maturation of synapses
Transfer of signals through cell membranes

Membrane cholesterol plays a vital role in the formation of amyloid-β.

Amyloid-β is a type of amino acid that is associated with the pathology of Alzheimer’s disease.

Cholesterol – Brain – Alzheimer Dementia: The ApoE Gene Connection

In adults, cholesterol is biosynthesized in the astrocyte cells (types of cells in the CNS).

The cholesterol is transported to the neurons via Apolipoprotein E lipoproteins (ApoE lipoproteins).

Synapse formation requires cholesterol transfer from the astrocytes to the neurons. This process is ApoE-dependent.

The ApoE gene helps produce the ApoE lipoprotein.

Mutations in the ApoE gene cause issues in ApoE lipoprotein production.

New Study Reveals Link Between Cholesterol Levels and Alzheimer’s Risk

In July 2023, research published in the American Academy of Neurology analyzed the relationship between fluctuating cholesterol levels and Alzheimer’s risk.

Study Design

The researchers picked 11,571 individual healthcare data of people over 60 for the study.

These individuals did not have a previous diagnosis of dementia or Alzheimer’s.

They were followed up for thirteen years to keep track of their fluctuating cholesterol levels and Alzheimer’s risk.

The participants were divided into five groups based on how much or how little their cholesterol and triglyceride variations were.

Study Results

In the thirteen years of follow-up, 2,473 subjects were diagnosed with Alzheimer’s or other forms of dementia.

The following variables that could affect the risk of developing dementia were adjusted while calculating the results.

Sex
Race
Education
Intake of lipid-lowering medications

The researchers observed that people in the high-fluctuating cholesterol category had a 19% increased risk of developing some form of dementia compared to the low-fluctuation group.

Similarly, individuals with the highest triglyceride fluctuations had a 23% increased risk of developing some form of dementia compared to the group with lower fluctuations.

Limitations

The mechanism behind how fluctuating cholesterol levels could increase Alzheimer’s risk is unclear.
There is no differentiation between Alzheimer’s and other different types of dementia.

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How To Keep Your Cholesterol Levels In Check?

Choosing The Right Diet

The following dietary changes can help bring down overall cholesterol and triglyceride levels.

Reduce intake of deep-fried foods and packaged snacks
Eliminate foods with high levels of trans and saturated fats
Increase intake of foods rich in soluble fiber and omega-3 fatty acids
Choose home-cooked meals over takeaways and restaurant meals

Physical Activity

When practiced regularly, low or moderate forms of aerobic exercises can help reduce overall cholesterol levels.

Losing Weight

Excess body fat is one of the common reasons for developing high cholesterol and triglyceride levels.

A 2004 systematic review reports that for every 10 kilograms of weight lost in obese and grossly overweight individuals, a drop of 0.23 mmol of cholesterol could be noticed.

Quitting Smoking

Smoking can increase overall cholesterol and triglyceride levels in the body.

Quitting smoking is critical for individuals with high cholesterol levels.

Cholesterol Lowering Medications

When lifestyle changes aren’t showing effects, or in the case of severely high cholesterol and triglyceride levels, medications to lower cholesterol levels may help.

Some of the common types of cholesterol-lowering medications include the following:

Statins
Cholesterol absorption inhibitors
Niacin
Fibrates
PCSK9 inhibitors

Does Good Cholesterol Decrease Your Risk Of Alzheimer’s Disease?

Many research studies report that increased High-Density Lipoprotein (HDL) levels may reduce the risk of Alzheimer’s disease.

HDL, also called good cholesterol, helps carry bad cholesterol from the bloodstream to the liver to help flush them out.

Animal-based studies report that higher levels of HDL may help protect against neuroinflammation and memory deficits.

Other studies report that HDL prevents the vascular accumulation of amyloid-β, a risk factor for developing Alzheimer’s disease.

Increasing HDL cholesterol levels and avoiding overall fluctuating cholesterol levels can reduce Alzheimer’s risk in older adults.

Summary: ApoE Alzheimer And Cholesterol Levels

Alzheimer’s is a type of dementia characterized by memory loss, behavioral changes, and poor judgment.
A 2023 study published in the American Academy of Neurology identifies a relationship between fluctuating cholesterol levels and Alzheimer’s risk.
According to this study, healthcare data from 11,571 older adults were collected, and these adults were followed up for thirteen years.
Individuals with the highest fluctuations in cholesterol and triglyceride levels had a 19 and 23% increased risk of developing dementia compared to those with the lowest fluctuations.
The researchers are still unsure why cholesterol fluctuations increase dementia risk and suggest further studies to understand this relationship better.
Eating heart-healthy foods, staying physically active, losing weight, and quitting smoking can all help bring down total cholesterol levels.
Other studies also report that an increase in High-Density Lipoprotein (HDL) levels may be beneficial in bringing down the risk of developing Alzheimer’s.