Protein build-up contributing to neurodegeneration
The accumulation of abnormal alpha-synuclein protein in the brain may be associated with the disruption of nerve cell communication, inflammation and progressive movement and/or cognitive decline.
Alpha-synuclein is a protein normally found inside nerve cells, where it is thought to play a role in helping cells communicate with one another. In conditions such as Parkinson's disease, Lewy body dementia and multiple system atrophy, alpha-synuclein can fold in an unusual way and clump together, forming abnormal deposits inside nerve cells or their surrounding support cells.
When alpha-synuclein builds up, it can form clumps known as Lewy bodies in neurons or spread within the brain's support cells (glial cytoplasmic inclusions), depending on the underlying condition. These deposits are one of the biological changes associated with Parkinson's disease and related conditions.
Importantly, some people can have alpha-synuclein changes in the brain without having noticeable movement or thinking symptoms, especially early on.
The effects of alpha-synuclein accumulation
Alpha-synuclein accumulation may be associated with:
- cognitive changes, including memory and thinking difficulties
- disruption of communication between nerve cells
- high blood pressure – particularly when longstanding or poorly controlled, as this contributes to small vessel damage over time
- loss of dopamine-producing nerve cells
- movement symptoms such as tremor, stiffness and slowness
- and in some conditions:
- autonomic symptoms, such as blood pressure or bladder changes
- visual hallucinations.
Alpha-synuclein changes may occur before noticeable symptoms develop in some people, sometimes appearing years before movement or cognitive symptoms, for example through sleep disturbances such as REM sleep behaviour disorder.
Common patient questions
Alpha-synuclein is strongly associated with Parkinson's disease and is thought to play a key role in the disease process, particularly in the loss of dopamine-producing nerve cells. However, Parkinson's disease likely involves multiple biological changes, and how these interact is still an active area of research.
Alpha-synuclein is linked to a group of conditions sometimes called 'synucleinopathies', including:
The pattern of where alpha-synuclein builds up in the brain, and how quickly it spreads differs across these conditions, which helps explain why they cause different combinations of symptoms. Not everyone with alpha-synuclein accumulation develops the same symptoms, and not all dementias involve alpha-synuclein.
Unlike some other proteins associated with neurodegeneration, there is currently no widely available brain scan that directly detects alpha-synuclein in living patients.
Diagnosis of alpha-synuclein-related conditions is usually based on clinical assessment; a specialist combines a person's history, examination and cognitive testing to reach a diagnosis, rather than relying on a single test.
Research into specific tests, including certain spinal fluid and skin biopsy techniques, is ongoing and showing significant promise.
Currently, there are no approved disease-modifying therapies in Australia that directly target alpha-synuclein. Existing treatments for Parkinson's disease and related conditions focus on managing symptoms, such as dopamine-based medication for movement symptoms, rather than addressing the underlying protein changes.
Research into alpha-synuclein-targeted therapies is ongoing.