Increase of soluble alpha-synuclein in a knock-in rat model of Alzheimer's disease
Alzheimer’s disease (AD), Parkinson’s disease (PD), and Lewy body dementia (LBD) are categorized under the umbrella term “Alzheimer’s disease and related dementias,” and can all exhibit alpha-synuclein (αSyn) pathology. Subjects with AD specifically display increases in soluble αSyn brain abundance compared to individuals who are not cognitively impaired. By contrast, there has been conflicting evidence as to whether soluble αSyn abundance is altered in transgenic animal models of AD, possibly due to differences in transgene expression, in promoters used to drive the expression of these transgenes, or in mouse background strains. To avoid these confounding variables, we use here amyloid precursor protein knock-in (App KI) rats to determine the brain abundance of soluble αSyn in animals modeling familial AD. We found that monomeric and oligomeric αSyn was increased in App KI rats as early as at 21 days of age, recapitulating findings in AD brains and suggesting that accumulation of αSyn species is an early event in the progression of AD.