Synucleinopathy

Synucleinopathies (also called α-Synucleinopathies) are neurodegenerative diseases characterized by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibers or glial cells.

There are three main types of synucleinopathy: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).

Other rare disorders, such as various neuroaxonal dystrophies, also have α-synuclein pathologies.

Synucleinopathies-related disorders such as Lewy body dementia (LBD) and Isolated REM sleep behavior disorder (iRBD) have been associated with neuroinflammation. Yu et al. examined whether the human leukocyte antigen (HLA) locus plays a role in iRBD and LBD. In iRBD, HLA-DRB1*11:01 was the only allele passing FDR correction (OR = 1.57, 95% CI = 1.27-1.93, p = 2.70e-05). We also discovered associations between iRBD and HLA-DRB1 70D (OR = 1.26, 95%CI = 1.12-1.41, p = 8.76e-05), 70Q (OR = 0.81, 95%CI = 0.72-0.91, p = 3.65e-04) and 71R (OR = 1.21, 95%CI = 1.08-1.35, p = 1.35e-03). Position 71 (pomnibus = 0.00102) and 70 (pomnibus = 0.00125) were associated with iRBD. The results suggest that the HLA locus may have different roles across synucleinopathy ¹⁾

Han SW, Park YH, Ryoo N, Kim K, Pyun JM, Kim S. Pearls & Oy-sters: Idiopathic Normal Pressure Hydrocephalus With Synucleinopathy: Diagnosis and Treatment. Neurology. 2021 Apr 30:10.1212/WNL.0000000000012099. doi: 10.1212/WNL.0000000000012099. Epub ahead of print. PMID: 33931530.

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Yu E, Krohn L, Ruskey JA, Asayesh F, Spiegelman D, Shah Z, Chia R, Arnulf I, Hu MTM, Montplaisir JY, Gagnon JF, Desautels A, Dauvilliers Y, Gigli GL, Valente M, Janes F, Bernardini A, Högl B, Stefani A, Ibrahim A, Heidbreder A, Sonka K, Dusek P, Kemlink D, Oertel W, Janzen A, Plazzi G, Antelmi E, Figorilli M, Puligheddu M, Mollenhauer B, Trenkwalder C, Sixel-Döring F, Cochen De Cock V, Ferini-Strambi L, Dijkstra F, Viaene M, Abril B, Boeve BF, Rouleau GA, Postuma RB; International LBD Genomics Consortium; Scholz SW, Gan-Or Z. HLA in isolated REM sleep behavior disorder and Lewy body dementia. Ann Clin Transl Neurol. 2023 Jul 4. doi: 10.1002/acn3.51841. Epub ahead of print. PMID: 37401389.