Apolipoprotein A1 as a potential biomarker for Parkinson's disease: A discussion with Mohammad Hadi Aarabi, MD

Background: There is an inverse relationship between high cholesterol levels and risk for Parkinson’s disease, thus suggesting that lipid metabolism underlies the pathogenesis of Parkinson’s disease. However, the roles of low-density level (LDL) and high-density lipoprotein (HDL) in Parkinson's disease are not apparent, given that statins are not neuroprotective. Recent studies have suggested that decreased apolipoprotein A1 (apo-A1) levels are associated with an earlier age of onset of Parkinson’s disease and increased dopaminergic vulnerability, according to a study performed by Mohammad Hadi Aarabi, MD, of the Basir Eye Health Research Center in Tehran, Iran and published in the April 2017 issue of the Journal of Neurology.

In contrast to the biochemical and genetic markers that have been identified for Alzheimer’s disease, few predictive markers exist for Parkinson’s disease. Because there is a significant loss of dopaminergic neurons prior to the clinical diagnosis of Parkinson’s disease (up to 50%), identification of such biomarkers is essential for prevention and treatment. Dr. Aarabi and colleagues have, for the first time, shown that the plasma apo-A1 level predicts microstructural changes in the white matter of patients with Parkinson’s disease.

MDLinx editors did an interview with Dr. Aarabi about this study and here is what he had to say.

MDLinx: If the apoA-1 level is low, are there any treatment modifications that should be considered?

Dr. Aarabi: Not yet! If patients' HDL in below optimal cutoff, then he should receive diet and/or medical intervention, but no specific treatment to modify Apo-A1 levels.

MDLinx: If the apoA-1 is normal, should a patient with Parkinson’s disease be retested?  If the apoA-1 level is low, should a patient with Parkinson’s disease be retested?

Dr. Aarabi: The novelty of our research does not rely on the fact that apo-A1 can predict risk for Parkinson’s disease or not. Thereby I assume that apo-A1 should be considered as a long-term modifier of Parkinson’s disease risk, perhaps through modifying white matter structures. So apo-A1 does not serve as a diagnostic bio-marker of Parkinson's disease.

MDLinx: Should diffusion-weighted imaging (DWI) connectometry be obtained in Parkinson’s disease patients with a low apoA-1 level? Is DWI connectometry a technique available to most community radiologists?

Dr. Aarabi: DWI sequence is now a common and point-of-care approach for detection of early stroke and similar brain pathologies. DWI connectometry is not!  Perhaps it is better to answer how accurate are the results. Connectometry is a new approach and perhaps the most accurate one in assessing white matter microstructure and detecting early degeneration such as in subgenual cingulum.

MDLinx: Can you comment on the association between statin use and risk for Parkinson’s disease?

Dr. Aarabi: Two big cohorts have yielded to contrasting results on the role of statins in Parkinson’s disease risk. Statins do not alter HDL as they do with LDL and are even less competent in lowering plasma triglycerides. Based on what we found, statins are incapable of altering Parkinson’s disease risk, at least not via apo-A1.

Dr. Aarabi is affiliated with the Basir Eye Health Research Center in Tehran, Iran. Dr. Farzaneh Rahmani, study co-author, is affiliated with the Neuroimaging Network of the Universal Scientific Education and Research Network in Tehran, Iran.