Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Acta Neuropathol ; 136(4): 589-605, 2018 10.
Article in English | MEDLINE | ID: mdl-29995210

ABSTRACT

α-Synuclein (αSyn) histopathology defines several neurodegenerative disorders, including Parkinson's disease, Lewy body dementia, and Alzheimer's disease (AD). However, the functional link between soluble αSyn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted αSyn in APP transgenic mice modeling AD and mouse primary neurons. Our results demonstrate bidirectional modulation of behavioral deficits and pathophysiology by αSyn. Overexpression of human wild-type αSyn in APP animals markedly reduced amyloid deposition but, counter-intuitively, exacerbated deficits in spatial memory. It also increased extracellular amyloid-ß oligomers (AßOs), αSyn oligomers, exacerbated tau conformational and phosphorylation variants associated with AD, and enhanced neuronal cell cycle re-entry (CCR), a frequent prelude to neuron death in AD. Conversely, ablation of the SNCA gene encoding for αSyn in APP mice improved memory retention in spite of increased plaque burden. Reminiscent of the effect of MAPT ablation in APP mice, SNCA deletion prevented premature mortality. Moreover, the absence of αSyn decreased extracellular AßOs, ameliorated CCR, and rescued postsynaptic marker deficits. In summary, this complementary, bidirectional genetic approach implicates αSyn as an essential mediator of key phenotypes in AD and offers new functional insight into αSyn pathophysiology.


Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Neurons/pathology , alpha-Synuclein/genetics , Alzheimer Disease/psychology , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Excitatory Postsynaptic Potentials , Gene Deletion , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Phosphorylation , Primary Cell Culture , Protein Conformation , tau Proteins/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...