'Good Cholesterol' Protective Against Alzheimer's?

Megan Brooks

April 21, 2022

Small high-density lipoprotein (HDL) particles in cerebrospinal fluid (CSF) may help protect against Alzheimer's disease (AD), new research suggests.

Results from a hypothesis-driven study showed that a higher number of small HDL particles in CSF was associated with better cognition and higher CSF levels of amyloid beta-42 (Aβ42), which have been linked to a lower risk for dementia.

"This study represents the first time that small HDL particles in the brain have been counted," study investigator Hussein Yassine, MD, Keck School of Medicine, University of Southern California, Los Angeles, noted in a news release.

"They may be involved with the clearance and excretion of the peptides that form the amyloid plaques we see in Alzheimer's disease, so we speculate that there could be a role for these small HDL particles in prevention," Yassine added.

The findings were published online April 13 in Alzheimer's & Dementia.

Brain Protection?

There has been abundant previous evidence that cardiovascular disease and cardiovascular risk factors play an important role in the etiology of AD, the investigators note. Small HDL particles have neuroprotective properties, but their association with cognition is unknown.

Using ion mobility analysis, the researchers identified, counted, and measured the size of individual small HDL particles in CSF and plasma from 180 healthy adults aged 60 years and older (mean age, 76.6 years).

A higher number of small HDL particles (7-10.5 nm) in CSF was positively associated with performance in three domains of cognitive function, independent of apolipoprotein E (APOE) ε4 status: age, sex, and years of education.

These associations were stronger in individuals without cognitive impairment, suggesting a role for small HDLs in prevention, the researchers note.

Higher levels of small HDL particles in CSF also correlated significantly with greater CSF Aβ42 levels.

Small HDL particles may reduce the risk of AD via their ability to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions, the investigators suggest.

"Confirmation of the role of small HDLs in the early stages of AD has important implications for AD prevention and management," they write.

"Measurements of neuroprotective small HDLs or its components in plasma and CSF could serve as biomarkers for guiding future clinical trials of AD prevention, and determination of their exchange between plasma and CSF could aid in the development of novel therapeutic agents," they add.

Going forward, the researchers aim to determine whether specific components of small HDL particles exchange across the blood, brain, and CSF barriers. They also want to develop approaches to potentially exploit small HDLs for therapeutic purposes.

The study was supported by the National Institutes of Health, the L.K. Whittier Foundation, the Huntington Medical Research Institutes, the Dairy Research Institute, Quest Diagnostics, SalioGen, the Della Martin Foundation, the Cure Alzheimer's Fund, the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, the Centers for Disease Control and Prevention, and Washington University. The Batey Foundation funded instrumentation used for ion mobility analysis. Yassine has reported no relevant financial relationships. A complete list of author disclosures is available in the original article.

Alzheimers Dement. Published online April 13, 2022. Full article

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