Novel blood serum assay to diagnose neurodegenerative diseases

Synucleinopathies are a group of neurodegenerative diseases caused by the abnormal accumulation a-synuclein, a protein normally found in the brain and neurons. Incorrect folding of α-synuclein leads to formation of ‘seeds’, which attract more α-synuclein proteins to form larger clumps. Although, α-synuclein seeds have been found in various tissues and blood of patients with synucleinopathies, its potential as a biomarker is ambiguous.

Recently, in a study published in Nature Medicine Japanese researchers present a novel assay that can efficiently detect α-synuclein seeds from a patient’s serum.

In this assay, named immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), the α-synuclein seeds are isolated from the patient’s serum through immunoprecipitation followed by rapid amplification by real-time quaking-induced conversion. This method is highly sensitive, as it can detect serum α-synuclein seed concentrations as small as 1000pg/ml. This comes as great news since most existing diagnostic methods require cerebrospinal fluid for synuclein detection.

The research team demonstrated that IP/RT-QuIC detected α-synuclein seeds efficiently in patients with neurodegenerative diseases and could distinguish them from people without degenerative diseases (controls). Next, they studied the structural properties of the amplified seeds using4 transmission electron microscopy. They observed that the synuclein seed structure varied with the type of synucleinopathy.5 Parkinson’s disease and dementia with Lewy bodies seeds showed paired filaments whereas MSA seeds had two distinct structures – twisted and straight filaments. This finding confirmed that IP/RT-QuIC coupled with TEM can differentiate between synucleinopathies based on disease specific seed structure.

Ref:Propagative α-synuclein seeds in the se are a group of neurodegenerative diseases caused by the abnormal accumulation α-synuclein, a protein normally found in the brain and neurons. Incorrect folding of α-synuclein leads to formation of ‘seeds’, which attract more α-synuclein proteins to form larger clumps.2 Although, α-synuclein seeds have been found in various tissues and blood of patients with synucleinopathies, its potential as a biomarker is ambiguous.

Recently, in a study published in Nature Medicine Japanese researchers present a novel assay that can efficiently detect α-synuclein seeds from a patient’s serum.

In this assay, named immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), the α-synuclein seeds are isolated from the patient’s serum through immunoprecipitation followed by rapid amplification by real-time quaking-induced conversion. This method is highly sensitive, as it can detect serum α-synuclein seed concentrations as small as 1000pg/ml. This comes as great news since most existing diagnostic methods require cerebrospinal fluid for synuclein detection.

3The research team demonstrated that IP/RT-QuIC detected α-synuclein seeds efficiently in patients with neurodegenerative diseases and could distinguish them from people without degenerative diseases (controls). Next, they studied the structural properties of the amplified seeds using4 transmission electron microscopy. They observed that the synuclein seed structure varied with the type of synucleinopathy.5 Parkinson’s disease and dementia with Lewy bodies seeds showed paired filaments whereas MSA seeds had two distinct structures - twisted and straight filaments. This finding confirmed that IP/RT-QuIC coupled with TEM can differentiate between synucleinopathies based on disease specific seed structure.

Reference:

Propagative α-synuclein seeds in the serum of patients with synucleinopathies,Nature Medicine, DOI 10.1038/s41591-023-02358-9