‘Different’ Lipid Profile Seen in Patients With GBA Mutations

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by Steve Bryson, PhD |

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Blood levels of various fat molecules — known as the lipid profile — in people with familial Parkinson’s disease caused by mutations in the GBA gene differ from those seen in people with sporadic Parkinson’s and healthy individuals, a study reported.

These findings suggested that problems with lipid metabolism (as seen in cholesterol and triglyceride levels) may influence disease development in this familial Parkinson’s group, its scientists noted.

The study, “Serum lipid profile among sporadic and familial forms of Parkinson’s disease,” was published in the journal NPJ Parkinson’s Disease.

Although the exact cause of Parkinson’s remains unclear, several genetic and environmental factors are thought to be involved. Through different metabolic pathways, these factors lead to the loss of nerve cells in the brain that produce the signaling molecule dopamine, resulting in Parkinson’s symptoms.

Altered cholesterol metabolism in the brain has been reported in people with this disease, and is considered a potential environmental factor. However, studies investigating bloodstream lipids — fats and fat-like substances carried in the blood — have reported mixed results in patients of different age groups and disease classifications.

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Several genes have been linked to familial forms of Parkinson’s, including LRRK2 and GBA, the two most common. Altered lipid metabolism has also been described in patients who carry mutations in these genes.

Based on these observations, scientists at the University of Seville in Spain wondered whether there were differences in the blood lipid profiles between people with sporadic Parkinson’s (having no apparent cause) and those with LRRK2 and GBA gene mutations.

“We hypothesized that levels of the serum lipids could be influenced by the genetic background of [Parkinson’s disease] patients,” the team wrote.

The study included 250 sporadic Parkinson’s patients, 27 others with GBA mutations (GBA-Parkinson’s) and 23 carrying LRRK2 mutations (LRRK2-Parkinson’s). A group of 420 healthy individuals was added as a control group.

Blood samples were collected to measure lipids such as total cholesterol, high-density lipoprotein (HDL, also known as “good” cholesterol) and low-density lipoprotein (LDL, “bad” cholesterol), and triglycerides.

Familial Parkinson’s patients were younger and had a lower age of onset than those with sporadic disease. More men were in the GBA-Parkinson’s group (73.91%), and more women in the LRRK2-Parkinson’s group (62.98%).

Despite a lower age of onset in the familial patients, no differences were evident in disease severity or treatment, or in co-existing conditions such as arterial hypertension (high blood pressure), diabetes, or hyperlipidemia (elevated lipids) among the groups.

All Parkinson’s patients grouped together had significantly lower mean total cholesterol, LDL, and triglycerides compared with controls. After adjusting for sex and age, total cholesterol and triglycerides remained significantly different. No differences in HDL was seen.

When comparing familial to sporadic cases, GBA-Parkinson’s had the lowest levels of total cholesterol, measured at a mean of 178.22 milligrams per deciliter (mg/dL), as well as LDL, 105.78 mg/dL. In contrast, LRRK2-Parkinson’s patients had the highest levels of both total cholesterol (213.73 mg/dL) and LDL (141.09 mg/dL).

In sporadic Parkinson’s patients, total cholesterol and LDL were lower compared to LRRK2-Parkinson’s and healthy individuals, but higher than GBA-Parkinson’s.

Higher triglycerides were seen in controls compared with all Parkinson’s groups, but after adjusting for sex and age, these differences were no longer statistically significant. Again, HDL was similar across all groups.

Notably, further analysis showed total cholesterol and LDL were lower in GBA-Parkinson’s versus LRRK2-Parkinson’s, but no differences were found in triglyceride levels or HDL.

Compared to sporadic patients, GBA-Parkinson’s had marginally significant lower LDL and less (not statistically significant) total cholesterol. Levels of total cholesterol and LDL were higher in LRRK2-Parkinson’s than in sporadic patients, but these differences did not reach statistical significance. No differences were seen in HDL and triglycerides between the familial and sporadic groups.

Finally, statistically significant differences in total cholesterol and LDL levels were evident between GBA-Parkinson’s patients and healthy controls. Triglyceride levels were lower only in sporadic Parkinson’s cases compared with controls, “suggesting that decreased triglyceride levels might be linked to sporadic forms of [Parkinson’s disease] rather than genetic forms,” the researchers wrote.

“In conclusion, our results show that GBA-associated [Parkinson’s disease] patients have different serum lipid profiles, and support the hypothesis of lipid metabolism disruption as one of the main pathogenic mechanisms in GBA-associated [Parkinson’s disease],” the team concluded.

“However, further investigations would be necessary to confirm these findings and to study their possible clinical implications.”

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