Regional levels of physiological α-synuclein are directly associated with Lewy body pathology
Lewy body (LB) pathology has been described as progressing through the brain in a stereotyped sequence, suggesting it may spread in a trans-synaptic manner similar to prion protein . A recent report demonstrated α-synuclein pathology in the deep cerebellar nuclei of LB disease cases . However, the cerebellar cortex is strongly connected with early predilection sites in the brainstem yet had virtually no α-synuclein pathology, indicating anatomical connectivity is not the sole determinant of vulnerability and cell- or region-autonomous factors may influence its development . A previous study in wild-type mice suggested an association between regional expression levels of physiological α-synuclein and vulnerability to LB pathology . However, no study has yet compared the expression of physiological α-synuclein across human brain regions and evaluated its relationship to α-synuclein pathology. Therefore, we sought to quantify regional expression levels of...
Tissue for this study was provided by Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council and by Brains for Dementia Research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK. D.E. is funded by Alzheimer’s Research UK.
Compliance with ethical standards
Conflict of interest
The authors declare they have no conflict of interest.
Ethical approval was granted by Newcastle University Ethics Board and the Joint Ethics Committee of Newcastle and North Tyneside Health Authority (ref: 08/H0906/136).