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P4–011: Effect of treadmill running on soluble beta‐amyloid concentrations in brains of young Tg2576 mice
Author(s) -
Jones Maria,
Zimmerman Scott,
Ehrenstrom Renee,
Cirrito John,
Restivo Jessica,
Timson Benjamin
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.1399
Subject(s) - treadmill , citrate synthase , medicine , environmental enrichment , endocrinology , chemistry , genetically modified mouse , biochemistry , transgene , enzyme , gene
Background: Alzheimer’s disease and Parkinson’s disease are the two most common neurodegenerative diseases, which are characterized by amyloid-beta (A b) plaques and alpha-synuclein (a-syn) rich Lewy bodies, respectively. An overlap of these two pathologies is found in patients with Lewy Body Dementia (LBD). Postmortem brains of LBD patients display significant synuclein accumulation in dystrophic neurites decorating A b plaques. Furthermore, in vitro studies report co-aggregation of Ab and a-syn, yet the precise role of a-syn in amyloid plaque formation remains elusive. Methods: In order to investigate a putative interaction of a-syn with amyloid plaque formation in vivo, we crossed APPPS1 with (Thy1)-[A30P]a-syn transgenic mice. Immunhistochemical and biochemical analysis revealed that a-syn affects amyloid plaque formation in vivo, whereas overall APP levels remain unaffected by the additional a-syn expression. Results: To further study the effect of a-syn on A b deposition, we performed cerebral stereotactic injections of 1) brain homogenate from aged APPPS1 transgenic mice into APPPS1x[A30P]a-syn transgenic mice and 2) a mixed preparation of brain homogenates from APPPS1 and (Thy1)-[A30P]a-syn transgenic mice into APPPS1 transgenic mice. We observed reduced seeding of Ab plaques under both experimental conditions, implying an inhibitory effect of a-syn on Ab plaque formation. Conclusions: In summary, our data suggest that a-syn plays an important role in Ab deposition. This work deepens our understanding of the complex pathophysiology of LBD and many other, related neurodegenerative diseases.