Clínic-IDIBAPS researchers, together with researchers from the University of Edinburgh, are leading a study that shows that detecting α-synuclein in the cerebrospinal fluid of people with REM sleep behavior disorder implies a high risk of developing Parkinson disease and Lewy body dementia.
Detection of this protein, which is found on the neurons of people with these neurodegenerative diseases, by means of a lumbar puncture constitutes a promising biomarker in the early stages of these diseases. Furthermore, it makes it possible to design studies against this protein to prevent these diseases from appearing.
The study, published in the journal The Lancet Neurology , was coordinated by Dr. Alex Iranzo, a neurologist with the Hospital Clínic Sleep Disorder Unit and head of the IDIBAPS Clinical neurophysiology group.
Parkinson disease and Lewy body dementia are incurable neurodegenerative diseases characterized by slow movement, stiffness, tremors, dementia, and hallucinations.
These symptoms are due to the accumulation of the protein α-synuclein on the neurons, in what are known as Lewy bodies. “Detecting the presence of this protein early on would make it possible to diagnose Parkinson disease and Lewy body dementia at a very early stage and trial drugs against this protein before the tremors, stiffness and dementia appear”, said Alex Iranzo.
It has been shown in people with Parkinson disease and Lewy body dementia that an ultrasensitive technique known as RT-QuIC can be used to detect abnormal α-synuclein aggregates in the cerebrospinal fluid of patients with high sensitivity.
The study published in The Lancet Neurology shows that RT-QuIC is equally sensitive and specific for detecting the protein in people with REM sleep behavior disorder who, years later, went on to develop Parkinson disease and Lewy body dementia.
Samples of cerebrospinal fluid were taken by means of a lumbar puncture from 52 patients with REM sleep behavior disorder and from 40 control subjects. The RT-QuIC test was positive in 90% of the people with REM sleep behavior disorder and in 10% of the controls.
All the participants in the study were followed up for more than 7 years. During this period, 62% of the patients were diagnosed with Parkinson disease or Lewy body dementia, of whom 97% had tested positive for α-synuclein at the start of the study. “During follow-up, none of the people in the control group developed either of the diseases; it was only developed by the patients with REM sleep behavior disorder", explained Alex Iranzo.
The study concludes that patients with REM sleep behavior disorder who test positive for α-synuclein had a very high risk of developing Parkinson disease and Lewy body dementia. Alpha-synuclein was detected up to 9 years before the clinical and pathologic diagnosis of the diseases. “We are looking at a highly valuable marker that allows us to identify people who will develop Parkinson disease and dementia linked to an accumulation of α-synuclein at a very early stage. This may help us to design therapeutic strategies that block the progress of this protein to the brain to prevent the onset of dementia and Parkinson", concluded Dr. Iranzo.
Detection of α-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study.
Iranzo A, Fairfoul G, Ayudhaya ACN, Serradell M, Gelpi E, Vilaseca I, Sánchez-Valle R, Gaig C, Santamaria J, Tolosa E, Riha RL, Green AJE.
Lancet Neurology 2021 Mar;20(3):203-212. doi: 10.1016/S1474-4422(20)30449-X.