RT Journal Article
SR Electronic
T1 Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-aggregation Stage in PD/DLB Pathology
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0217-18.2018
DO 10.1523/ENEURO.0217-18.2018
VO 5
IS 4
A1 Kyota Fujita
A1 Hidenori Homma
A1 Kanoh Kondo
A1 Masashi Ikuno
A1 Hodaka Yamakado
A1 Kazuhiko Tagawa
A1 Shigeo Murayama
A1 Ryosuke Takahashi
A1 Hitoshi Okazawa
YR 2018
UL http://www.eneuro.org/content/5/4/ENEURO.0217-18.2018.abstract
AB Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) reflects neurite degeneration at the early stage of Alzheimer’s disease (AD), before extracellular Aβ aggregates are histologically detectable. Here, we demonstrate that similar changes in MARCKS occur in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) pathologies in both mouse models and human patients. The increase in the level of pSer46-MARCKS began before α-synuclein aggregate formation, at a time when human α-Syn-BAC-Tg/GBA-hetero-KO mice exhibited no symptoms, and was sustained during aging, consistent with the pattern in human postmortem brains. The results strongly imply a common mechanism of pre-aggregation neurite degeneration in AD and PD/DLB pathologies.