Hu, X.Hu, Z.L.Li, Z.Ruan, C.S.Qiu, W.Y.Pan, A.Li, C.Q.Cai, Y.Shen, L.Chu, Y.Tang, B.S.Cai, H.Zhou, X.F.Ma, C.Yan, X.X.2021-09-282021-09-282017Frontiers in Neuroanatomy, 2017; 11:45-1-45-191662-51291662-5129https://hdl.handle.net/2440/132359Genetic variations in the vacuolar protein sorting 10 protein (Vps10p) family have been linked to Alzheimer's disease (AD). Here we demonstrate deposition of fragments from the Vps10p member sortilin at senile plaques (SPs) in aged and AD human cerebrum. Sortilin changes were characterized in postmortem brains with antibodies against the extracellular and intracellular C-terminal domains. The two antibodies exhibited identical labeling in normal human cerebrum, occurring in the somata and dendrites of cortical and hippocampal neurons. The C-terminal antibody also marked extracellular lesions in some aged and all AD cases, appearing as isolated fibrils, mini-plaques, dense-packing or circular mature-looking plaques. Sortilin and β-amyloid (Aβ) deposition were correlated overtly in a region/lamina- and case-dependent manner as analyzed in the temporal lobe structures, with co-localized immunofluorescence seen at individual SPs. However, sortilin deposition rarely occurred around the pia, at vascular wall or in areas with typical diffuse Aβ deposition, with the labeling not enhanced by section pretreatment with heating or formic acid. Levels of a major sortilin fragment ~15 kDa, predicted to derive from the C-terminal region, were dramatically elevated in AD relative to control cortical lysates. Thus, sortilin fragments are a prominent constituent of the extracellularly deposited protein products at SPs in human cerebrum.en© 2017 Hu, Hu, Li, Ruan, Qiu, Pan, Li, Cai, Shen, Chu, Tang, Cai, Zhou, Ma and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Alzheimer’s disease; amyloid deposition; neuritic plaques; synaptic pathology; Vps10p family proteinsJournal article10.3389/fnana.2017.000452021-09-28562703Zhou, X.F. [0000-0002-8687-0175]