Increased Lipid Levels Could Be Early Presentation of Parkinson's

As stated in article published recently in the clinical journal Neurobiology of Aging, a collaborative team of researchers has discovered that elevated levels of certain types of lipids in the brain could be an early presentation of Parkinson’s disease.

Authored by researchers at McLean Hospital, a Harvard Medical School affiliate, and Oxford University, the article, “Glycosphingolipid levels and glucocerebrosidase activity are altered in normal aging of the mouse brain,” suggests that these new findings could have significant implications for early identification of patients who may be at risk for developing Parkinson’s disease, leading to earlier treatment.¹

Parkinson’s disease is a degenerative, progressive disorder characterized by the dramatic reduction of nerve cells, specifically dopamine neurons in the substantia nigra area of the brain; these cells play a critical role in the initiation of movement. Historically, the loss of these nerve cells has been credited to the toxic accumulation of the alpha-synuclein protein. Over the past 15 years; however, researchers have been studying the potential relationship between the risk of developing Parkinson’s and lysosomal storage diseases—particularly Gaucher disease, which is the result of mutations that lead to loss of function in the glucocerebrosidase (GBA) gene.

Typically, the GBA gene manufactures an enzyme that breaks down lipids. In the childhood disorder Gaucher disease, though, a near complete lack of this enzyme activity results in life-threatening elevations of lipids inside cells.

Ole Isacson, MD, PhD, professor of Neurology and Neuroscience at Harvard Medical School, co-director of the Neuroregeneration Research Institute at McLean Hospital, served as the co-senior author of the study. "[These findings] mean that lipid accumulation may also be important in PD, and scientists at the Neuroregeneration Research Institute at McLean Hospital have previously shown that there is an elevation of a class of lipids, called glycosphingolipids, in the substantia nigra of patients with PD," he said.

The teams of researchers collaborated using young and old mice to measure the levels of glycosphingolipids in the aging brain since aging is the most significant risk factor for developing Parkinson’s.

It was discovered that the same glycosphingolipids that are heightened in the brains of Parkinson's disease patients are also increased in the brains of aging mice. These findings prove that both genetics and aging can cause similar lipid elevations in the brain that are exhibited in Parkinson's disease pathology.

"These results lead to a new hypothesis that lipid alterations may create a number of problems inside nerve cells in degenerative aging and Parkinson's disease, and that these changes may precede some of the more obvious hallmarks of Parkinson's disease, such as protein aggregates," said Penny Hallett, PhD, study lead author and co-director of McLean's Neuroregeneration Research Institute. "This potentially provides an opportunity to treat lipid changes early on in Parkinson's disease and protect nerve cells from dying, as well as the chance to use the lipid levels as biomarkers for patients at risk."

For more new discoveries from the rare disease community, follow Rare Disease Report on Facebook and Twitter.

References:

1. Penelope J. Hallett, Mylene Huebecker, Oeystein R. Brekk, Elizabeth B. Moloney, Emily M. Rocha, David A. Priestman, Frances M. Platt, Ole Isacson. Glycosphingolipid levels and glucocerebrosidase activity are altered in normal aging of mouse brain. Neurobiology of Aging, 2018; DOI: 10.1016/j.neurobiolaging.2018.02.028