Sleep disturbance is a precursor to neurodegenerative diseases such as Parkinson’s disease.

Recent research definitively confirms that isolated REM sleep behavior disorder (the stage of sleep in which a person makes rapid eye movements) is an early stage of neurodegenerative diseases associated with the alpha-synuclein protein, such as Parkinson’s disease.

The study was carried out by specialists from the Hospital Clinic and the Biomedical Research Institute of August Pi and Sunier (IDIBAPS), both institutions are located in Barcelona.

Evidence came from studies of postmortem brain tissue. This is the first study with the largest number of cases to confirm this relationship in detail and definitively.

The results of the new study offer a strong basis for developing clinical trials of treatments aimed at altering the development of these neurodegenerative diseases by targeting alpha-synuclein.

Diseases such as Parkinson’s disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are some of the synucleinopathies that can occur or be detected in the early stages due to isolated REM sleep behavior disorder (iRBD, its acronym in English ). ).

The study was led by Dr. Alex Iranzo, Head of the Sleep Disorders Unit at the Hospital Clínic and Head of the Clinical Neurophysiology Group at IDIBAPS, together with Dr. Gérard Maia, a neurologist and researcher in the same team. The event was also attended by Dr. Raquel Sanchez-Valle, medical director of the hospital clinic and head of the Alzheimer’s disease and other cognitive disorders group at IDIBAPS, as well as researchers from the IDIBAPS Neurological Tissue Bank.

Dr. Gerard Maia (left) and Dr. Alex Iranzo (right). (Photo: Hospital Clinic / IDIBAPS)

iRBD is a sleep disorder characterized by nightmares and abnormal sleep behaviors, such as screaming or punching, associated with REM sleep without muscle relaxation. The same group of researchers previously considered the disorder to be a precursor to neurodegenerative diseases in a study that began in 2006. However, until now there has been a lack of definitive evidence that could confirm its connection with serious disorders such as Parkinson’s disease or Lewy body dementia.

The study suggests that early detection of iRBD may serve as a key biomarker for the progression of alpha-synucleinopathies, which is important for early detection and clinical intervention.

For this purpose, the postmortem brain and spinal cord of 20 patients diagnosed with iRDD were examined in detail, the tissues of which were transferred for analysis to the IDIBAPS Neurological Tissue Bank. The results demonstrate a clear association between iRBD and alpha-synuclein accumulation in several brain regions, indicating that it is a very early sign of neurodegeneration.

One of the most revealing findings of the study was the discovery of alpha-synuclein deposits in brain regions critical for the regulation of REM sleep, including the stratum coeruleus complex, nucleus reticularis gigantocellularis, laterodorsal tegmentum, and amygdala. These regions are responsible for controlling muscle atonia or relaxation during REM sleep, and their dysfunction is known to be associated with the development of typical involuntary movements during iRBD sleep.

In patients who did not develop symptoms of dementia or parkinsonism, alpha-synuclein deposits were localized to the brainstem and limbic system. However, in patients who developed Parkinson’s disease or dementia with Lewy bodies, alpha-synuclein deposits were much more extensive, indicating progression of the disease toward more widespread neuronal damage.

“These results are consistent with previous studies suggesting that iRBD may be an early manifestation of synucleinopathies, but this study provides the strongest neuropathological evidence to date,” explains Gérard Maia. Additionally, the researchers found that alpha-synuclein deposits were present not only in neurons, but also in glial cells (astrocytes and oligodendrocytes), suggesting that glia also play a key role in disease progression.

Another observation from the study is the identification of a range of coexisting pathologies that affect the majority of people with iRBD. “In particular, we observed a high prevalence of neuropathological changes typical of Alzheimer’s disease. All 20 iRBD patients had alpha-synuclein in their brains. But 70% showed pathological characteristics associated with Alzheimer’s disease, which may indicate that iRBD may be associated with a higher risk of developing Alzheimer’s disease, although its significance is still unclear,” says Gerard Maia.

The results of this study have important implications for future diagnosis and treatment of people with iRBD and these neurodegenerative diseases. First, the study provides evidence that alpha-synuclein deposits in brain structures involved in REM sleep may serve as early biomarkers for identifying people at risk of developing neurodegenerative diseases such as Parkinson’s disease and dementia with Lewy body defects.

In addition, identifying multiple coexisting pathologies opens up new opportunities for developing treatments that target not only alpha-synuclein, but also other pathological proteins, such as beta-amyloid and tau, that may influence the progression of parkinsonism and dementia. The study suggests that clinical trials targeting combination treatments of different pathological proteins may be a promising strategy for preventing or delaying the onset of Parkinson’s disease and dementia in people with iRBD.

The study is titled “Post-mortem Neuropathology of Idiopathic Rapid Eye Movement Sleep Behavior Disorder: A Case Series.” And it was published in the academic journal The Lancet Neurology. (Source: Hospital Clinic / IDIBAPS)