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alpha synuclein aggregates in CSF; real-time quaking-induced conversion (RT-QuIC)

Indications: - evaluation of inherited Parkinson's disease - 90% sensitivity & 80% specificity - evaluation for prodromal alpha-synucleinopathies [2] * high sensitivity & specificity in detecting underlying Lewy body pathology in those with mild cognitive impairment [3] Procedure: - CSF real-time quaking-induced conversion (RT-QuIC) [1] - CSF seed amplification assay of alpha-synuclein multiplexed with an enzyme-linked immunosorbent assay (ELISA) [5] Clinical significance: - 90% sensitive & specific for development of Parkinson's disease or Lewy body dementia in patients with rapid eye movement sleep behavioral disorder [2] - CSF alpha-synuclein seeding activity correlates with clinical features of Lewy body dementia [6] - 89% sensitivity & 96% specificity for a diagnosis of Parkinson's disease [4] - sensitivity for multiple system atrophy is 75% [4] - sensitivity for idiopathic REM sleep behavior disorder is 64% [4] - sensitivity of 92% & specificity of 85% for CSF seed amplification assay in differentiating Parkinson's disease patients from controls [5] Notes: - test also positive in 40% of LRRK2 p.G2019S carriers & 20% of normal controls

Related

alpha-synuclein; non-A beta component of AD amyloid; non-A4 component of amyloid; NACP (SNCA, NACP, PARK1)

General

alpha synuclein Ag in tissue

References

  1. Garrido A, Fairfoul G, Tolosa ES et al. alpha-synuclein RT-QuIC in cerebrospinal fluid of LRRK2-linked Parkinson's disease. Ann Clin Transl Neurol 2019 May 9; 6:1024. PMID: 31211166 Free PMC Article
  2. George J CSF Biomarker Flags Parkinson's Pathology Years Before Symptoms Appear. Strong sensitivity, specificity in early study. MedPage Today March 4, 2021 https://www.medpagetoday.com/neurology/parkinsonsdisease/91484 - Iranzo A, Fairfoul G, Ayudhaya ACN et al Detection of alpha-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study. Lancet Neurology 2021 PMID: 33609478 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30449-X/fulltext - Zerr I RT-QuIC for detection of prodromal alpha-synucleinopathies Lancet Neurology 2021 PMID: 33609466 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00036-3/fulltext
  3. Rossi M, Baiardi S, Teunissen CE et al. Diagnostic value of the CSF alpha-synuclein real-time quaking-induced conversion assay at the prodromal MCI stage of dementia with Lewy bodies. Neurology 2021 Jul 1; [e-pub]. PMID: 34210822 PMCID: PMC8408510 Free PMC article https://n.neurology.org/content/97/9/e930
  4. Poggiolini I et al. Diagnostic value of cerebrospinal fluid alpha-synuclein seed quantification in synucleinopathies. Brain 2021 Dec 11; [e-pub]. PMID: 34894214 Free article https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab431/6459775
  5. Majbour N et al. Disease-associated alpha-synuclein aggregates as biomarkers of Parkinson disease clinical stage. Neurology 2022 Sep 12; [e-pub] isease-associated alpha-synuclein aggregates as biomarkers of Parkinson https://n.neurology.org/content/early/2022/09/12/WNL.0000000000201199
  6. Coughlin DG et al. Association of CSF alpha-synuclein seeding amplification assay results with clinical features of possible and probable dementia with Lewy bodies. Neurology 2024 Aug 13; 103:e209656. PMID: 39013126 PMCID: PMC11238940 (available on 2025-08-13) https://www.neurology.org/doi/10.1212/WNL.0000000000209656

Components

alpha-synuclein seed amplification assay; CSF alpha-synuclein (SYNTap test)