TY - JOUR T1 - Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre-Aggregation Stage in PD/DLB Pathology JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0217-18.2018 SP - ENEURO.0217-18.2018 AU - Kyota Fujita AU - Hidenori Homma AU - Kanoh Kondo AU - Masashi Ikuno AU - Hodaka Yamakado AU - Kazuhiko Tagawa AU - Shigeo Murayama AU - Ryosuke Takahashi AU - Hitoshi Okazawa Y1 - 2018/08/16 UR - http://www.eneuro.org/content/early/2018/08/16/ENEURO.0217-18.2018.abstract N2 - Phosphorylation of MARCKS (myristoylated alanine-rich C kinase substrate) 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 body (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.Significance Statement: At early stage of Alzheimer’s disease before the aggregation of extracellular Aβ, phosphorylation of MARCKS at Ser46 reflects neurite degeneration. In this study, we confirmed the similar changes both in mouse models and human patients of Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). Phosphorylation of MARCKS at Ser46 was increased before α-synuclein aggregation was detected, and the increase of pSer46-MARCKS was sustained during aging. These results suggest that neurite degeneration detected by pSer46-MARCKS is a common pre-aggregation mechanism shared by AD and PD/DLB pathologies. ER -