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synucleinopathy (includes alpha-synucleinopathy)

Diverse group of disorders characterized by abnormal deposition of alpha-synuclein, includes: - Parkinson's disease - dementia with Lewy bodies - multiple system atrophy - pure autonomic failure - neuroaxonal dystrophies - pantothenate kinase associated neurodegeneration - subacute sclerosing panencephalitis - some Alzheimer's disease, aging, Down's syndrome Clinical manifestations: - REM sleep disorder may precede synucleinopathy by 50 years [3] - strongest predictor of alpha-synucleinopathy [4] - see specific synucleinopathy Laboratory: - alpha synuclein aggregates in CSF (RT-QuIC test) - neuronally derived extracellular vesicle alpha-synuclein Ag in serum may serve as a biomarker for prediction of alpha-synucleinopathies [4] - skin biopsy detects cutaneous phosphorylated alpha-synuclein in 96% of patients with synucleinopathy [5] Differential diagnosis: 1) other disorders which may also have alpha-synuclein deposits a) motor neuron disease b) amyotrophic lateral sclerosis c) amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam d) tauopathies 1] frontotemporal dementia 2] Pick's disease 3] progressive supranuclear palsy 4] corticobasal degeneration e) prion diseases f) ataxia telangiectasia g) Meige's syndrome 2) pathologic structures containing alpha synuclein deposits: a) Lewy bodies b) glial and neuronal cytoplasmic inclusions (multiple system atrophy) c) axonal spheroids (pantothenate kinase associated neurodegeneration)

Interactions

disease interactions

Specific

Hallervorden-Spatz disease; pantothenate kinase associated neurodegeneration (PKAN); neurodegeneration with brain iron accumulation type 1 (NBIA1); pigmentary pallidal degeneration Lewy body dementia Lewy body variant of Alzheimer's disease (AD) multiple system atrophy (MSA) Parkinson's disease (paralysis agitans, PD) pure autonomic failure (PAF)

General

neurodegenerative disease

References

  1. Marti, et al. Mov Disord. 2003 Sep;18 Suppl 6:S21-7. PMID: 14502652
  2. Jellinger KA. Mov Disord. 2003 Sep;18 Suppl 6:S2-12. PMID: 14502650
  3. Claassen DO et al REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010 Aug 10;75(6):488-9. PMID: 20668263
  4. Yan S, Chang C, Janzen A et al. Neuronally derived extracellular vesicle alpha-synuclein as a serum biomarker for individuals at risk of developing Parkinson disease. JAMA Neurol 2024 Jan 1; 81:59-68. PMID: 38048087 PMCID: PMC10696516 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2812433
  5. George J Skin Test Detects Parkinson's and Other Synucleinopathies. Cutaneous alpha-synuclein deposits may serve as a biomarker. MedPage Today March 21, 2024 https://www.medpagetoday.com/neurology/parkinsonsdisease/109309 - Gibbons CH, Levine T, Adler C et al Skin Biopsy Detection of Phosphorylated alpha-Synuclein in Patients With Synucleinopathies. JAMA. Published online March 20, 2024. PMID: 38506839 https://jamanetwork.com/journals/jama/fullarticle/2816441