Low Cholesterol in Cells’ Lipid Rafts May Add to Behavioral Differences

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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low cholesterol in lipid rafts | Fragile X News Today | illustration of researcher in lab using microscope

Unusually low amounts of cholesterol in cellular structures called lipid rafts may contribute to behavioral differences seen in people with fragile X syndrome, a new study indicates.

“The correlation between [lipid rafts] cholesterol and the clinical profile showed a significant association with autistic traits,” the researchers wrote.

The study, “Association of lipid rafts cholesterol with clinical profile in fragile X syndrome,” was published in Scientific Reports.

Every cell in the body has a cellular membrane —a wall of fats and proteins that separates the inside of the cell from the rest of the world. Lipid rafts, or LRs, are cholesterol-rich structures that form in cellular membranes, and play important roles in facilitating communication among cells. In particular, lipid rafts are important for the function of neurons (nerve cells).

“In neurons, LRs serve as ordered platforms that coordinate signaling molecules through membrane receptors and are involved in synaptic transmission [communication between neurons],” the researchers wrote.

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Study Links Autism Spectrum Disorders, Including Fragile X, to Low Cholesterol Levels

Fragile X is the most common cause of inherited intellectual disability and autism spectrum disorders, and is characterized by developmental and behavioral abnormalities. These presumably arise due to differences in neuronal functioning, but the details remain incompletely understood.

Many people with fragile X exhibit lower-than-normal cholesterol levels in their plasma, which is the non-cell part of blood.

“Specifically, 90% of [fragile X syndrome] individuals have plasma cholesterol below the 50th centile of the normalized population and up to 30% fulfill the criteria of hypocholesterolemia [clinically significant low cholesterol levels],” the researchers wrote.

Abnormalities in these levels have been linked to changes in LR biology in other neurological disorders. However, LRs in fragile X have not been thoroughly studied.

“This study thus aims to explore the lipid content of LRs in platelets of [fragile X] individuals as compared to healthy individuals,” the scientists wrote. “We also investigated the relation of LRs cholesterol with lipid profile and cognitive functions in [fragile X syndrome].”

The researchers analyzed blood samples from 27 people with fragile X, as well as 25 people without the condition (controls). The fragile X patients also underwent a battery of cognitive and behavioral assessments.

To assess lipid rafts, the researchers examined the membranes of platelets, which are cell fragments in the blood that are important for clotting, among other processes. The LRs in platelets are considered a plausible surrogate for studying nerve cells, since “platelets express many receptors and markers that are also found in neurons and thus may recapitulate the defects observed in [fragile X syndrome] neurons,” the scientists wrote.

Results showed that Average LR cholesterol levels were lower in fragile X patients than in controls, but the difference was not statistically significant. Of note, LR cholesterol levels were significantly correlated with serum cholesterol levels in fragile X patients, but the two levels were not significantly associated in the controls.

The researchers conducted statistical analyses to look for connections between LR cholesterol levels and various behavioral metrics.

Fragile X patients with higher levels tended to have higher scores on the Adaptive Behavior Assessment System (ABAS), the results showed. This indicates that higher cholesterol levels are associated with better adaptive behavior — that is, a greater ability to live independently and function in day-to-day life.

Higher cholesterol levels also were significantly linked with less severe autistic behaviors, as measured by the Social Communication Questionnaire (SCQ).

Based on these associations, the researchers hypothesized that “a reduction of cholesterol content in LRs might contribute to [fragile X] pathophysiology [disease processes] and ultimately to clinical profile.”

“Taken together, these findings suggest a potential mechanistic implication of low cholesterol in cognitive dysfunction of [fragile X] individuals probably through disruption of cholesterol content in LRs,” they concluded.

The team stressed a need for further research to validate these findings.