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Selective insolubility of alpha-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model.

Authors: Kahle, PJ  Neumann, M  Ozmen, L  Muller, V  Odoy, S  Okamoto, N  Jacobsen, H  Iwatsubo, T  Trojanowski, JQ  Takahashi, H  Wakabayashi, K  Bogdanovic, N  Riederer, P  Kretzschmar, HA  Haass, C 
Citation: Kahle PJ, etal., Am J Pathol. 2001 Dec;159(6):2215-25.
Pubmed: (View Article at PubMed) PMID:11733371

alpha-Synuclein (alpha-SYN) is deposited in intraneuronal cytoplasmic inclusions (Lewy bodies, LBs) characteristic for Parkinson's disease (PD) and LB dementias. alpha-SYN forms LB-like fibrils in vitro, in contrast to its homologue beta-SYN. Here we have investigated the solubility of SYNs in human LB diseases and in transgenic mice expressing human wild-type and PD-associated mutant [A30P]alpha-SYN driven by the brain neuron-specific promoter, Thy1. Distinct alpha-SYN species were detected in the detergent-insoluble fractions from brains of patients with PD, dementia with LBs, and neurodegeneration with brain iron accumulation type 1 (formerly known as Hallervorden-Spatz disease). Using the same extraction method, detergent-insolubility of human alpha-SYN was observed in brains of transgenic mice. In contrast, neither endogenous mouse alpha-SYN nor beta-SYN were detected in detergent-insoluble fractions from transgenic mouse brains. The nonamyloidogenic beta-SYN was incapable of forming insoluble fibrils because amino acids 73 to 83 in the central region of alpha-SYN are absent in beta-SYN. In conclusion, the specific accumulation of detergent-insoluble alpha-SYN in transgenic mice recapitulates a pivotal feature of human LB diseases.

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CRRD Object Information
CRRD ID: 6480103
Created: 2012-03-13
Species: All species
Last Modified: 2012-03-13
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.