Boston: High levels of certain types of fat molecules in the brain may be an early sign of Parkinson's disease, a study has found.
The finding could have significant implications for identifying patients who may be at risk for developing Parkinson's disease, and for the early treatment of the disease.
Parkinson's disease (PD) is a degenerative, progressive disorder characterised by the dramatic reduction of nerve cells, particularly dopamine neurons that are involved in movement initiation, in an area of the brain called the substantia nigra.
For many years now, the loss of these nerve cells has been attributed to the toxic accumulation of the protein alpha-synuclein.
In the past 15 years, however, researchers have been studying an interesting relationship between the risk of developing PD and a group of disorders called lysosomal storage diseases - particularly Gaucher disease, which is caused by mutations that lead to loss of function in the glucocerebrosidase (GBA) gene.
The GBA gene normally produces an enzyme that breaks down lipids, but in the childhood disorder Gaucher disease, a near total lack of this enzyme activity leads to massive and usually fatal elevations of lipids inside cells.
Notably, people who do not develop Gaucher disease, but are carriers of one defective gene copy, have a 7 to 10-fold risk of developing PD with age.
"This means that lipid accumulation may also be important in PD, and scientists have previously shown that there is an elevation of a class of lipids, called glycosphingolipids, in the substantia nigra of patients with PD," said Ole Isacson, professor at Harvard Medical School in the US.
Since aging is the most significant risk factor for developing PD, researchers from McLean Hospital in the US and the University of Oxford in the UK collaborated to measure the levels of glycosphingolipids in the aging brain, using young and old mice.
They found that the same glycosphingolipids that are increased in the brains of Parkinson's disease patients are also elevated in the brains of aging mice.
These findings show that both genetics (GBA gene mutation) and aging can cause the same lipid elevations in the brain that are demonstrated 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, lead author of the study published in the journal Neurobiology of Aging.
"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," Hallett said.
