Research article

Lack of α-synuclein increases amyloid plaque accumulation in a transgenic mouse model of Alzheimer's disease

Verena Kallhoff^1,2 , Erica Peethumnongsin^1,3 and Hui Zheng^1,2,3

¹  Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA

²  Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA

³  Interdepartmental Program of Cellular and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA

author email corresponding author email

Molecular Neurodegeneration 2007, 2:6doi:10.1186/1750-1326-2-6

Published:	16 March 2007

Abstract

α-synuclein is a small soluble, cytosolic protein which associates with vesicular membranes. It is a component of intracellular Lewy bodies present in Parkinson's disease and a subset of Alzheimer's disease (AD). In addition, early studies identified a fragment of α-synuclein in the amyloid plaques of AD patients. Hypothesizing that α-synuclein might modify the AD pathogenic process, we crossed the Tg2576 strain of APP transgenic mice onto an α-synuclein knockout background to determine the effects of α-synuclein on Aβ production and plaque deposition. We found that α-synuclein deficiency does not affect the Aβ levels, nor does it alter the age of onset of plaque pathology. To our surprise, however, loss of α-synuclein leads to a significant increase in plaque load in all areas of the forebrain at 18 months of age. This is associated with an increase in another synaptic protein, synaptophysin. We thus conclude that α-synuclein is not involved in seeding of the plaques, but rather suppresses the progression of plaque pathology at advanced stages.