This report describes Lewy body dementia, SNCA-related, which is a subtype of Lewy body dementia (see MIM:127750); this disease exhibits autosomal dominant inheritance. The human gene implicated in this disease, SNCA (α-synuclein), is also implicated in Parkinson disease 1 (FBhh0000006). SNCA encodes a protein that is abundant in neurons, including the brain. It appears to play several roles, including regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. α-synuclein protein is the primary structural component of the Lewy body aggregates typically found in the brains of patients with Lewy body dementia and Parkinson disease.
No gene orthologous to SNCA has been identified in Drosophila.
Multiple different UAS constructs of the human Hsap\SNCA gene have been introduced into flies, including wild-type SNCA and genes carrying mutational lesions implicated in PARK1; one of these is also implicated in Lewy body dementia. Variant(s) implicated in human disease tested (as transgenic human gene, SNCA): the E46K variant form of the human gene has been introduced into flies.
[updated Mar. 2019 by FlyBase; FBrf0222196]
LBD is a chronic, neurodegenerative cognitive disorder; it is the 3rd most common form of dementia (https://parkinsonsdisease.net/clinical/lewy-body-dementia-differences/).
Because symptoms of Lewy body dementia can closely resemble other more commonly known disorders like Alzheimer disease and Parkinson disease, it is often underdiagnosed or misdiagnosed. in LBD, dementia appears first or around the same time as parkinsonism. In contrast, for dementia associated with Parkinson disease, dementia develops after several or many years of living with Parkinson disease. (https://www.davisphinneyfoundation.org/blog/difference-lewy-body-dementia-parkinsons-disease-alzheimers-disease/)
Dementia with Lewy bodies (DLB) is a neurodegenerative disorder clinically characterized by dementia and parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication (McKeith et al., 1996, pubmed:8909416; Mizutani, 2000, pubmed:11068444; McKeith et al., 2005, pubmed:16237129). [from MIM:127750; 2019.06.03]
Dementia with Lewy bodies (DLB) can be caused by mutation in the alpha-synuclein (SNCA) or beta-synuclein (SNCB) genes. DLB exhibits autosomal dominant inheritance. [from MIM:127750; 2019.06.03]
The variable locations of Lewy bodies observed in the brain correlate with the different diseases associated with this pathology (Parkinson, Parkinson dementia, and Lewy body dementia) (https://www.apdaparkinson.org/article/understanding-parkinsons-disease-dementia-lewy-bodies/).
At autopsy, SNCA-positive Lewy body protein aggregates are observed within neurons of the brain; Lewy bodies are present in a pattern more widespread than usually observed in Parkinson disease. For diagnosis, brainstem or cortical Lewy bodies are the only essential pathologic features. (McKeith et al., 1996, pubmed:8909416; Mizutani, 2000, pubmed:11068444; McKeith et al., 2005, pubmed:16237129) [from MIM:127750; 2019.06.03]
The SNCA protein plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. It participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion, and dilation of exocytotic fusion pores. It also acts also as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of SNARE synaptic fusion components at presynaptic plasma membrane; this chaperone activity is important to sustain normal SNARE-complex assembly during aging. [Gene Cards, SNCA; 2019.06.03]
One of several diseases collectively described as synucleinopathies; there has recently been developed a skin biopsy that allows early detection of phosphorylated α-synuclein in patients with synucleinopathies (Gibbons et al., 2024; pubmed:38506839).
Alpha-synuclein is a highly conserved protein that is abundant in neurons, especially presynaptic terminals. [from MIM:163890; 2019.06.03]
No gene orthologous to SNCA has been identified in Drosophila.
