PMID- 22998035 OWN - NLM STAT- MEDLINE DCOM- 20131028 LR - 20211021 IS - 1750-3639 (Electronic) IS - 1015-6305 (Print) IS - 1015-6305 (Linking) VI - 23 IP - 3 DP - 2013 May TI - Secretory sorting receptors carboxypeptidase E and secretogranin III in amyloid beta-associated neural degeneration in Alzheimer's disease. PG - 274-84 LID - 10.1111/j.1750-3639.2012.00644.x [doi] AB - The secretory sorting receptors carboxypeptidase E (CPE) and secretogranin III (SgIII) critically activate peptidic messengers and targeting them at the regulated secretory pathway. In Alzheimer's disease (AD), the wide range of changes includes impaired function of key secretory peptidic cargos such as brain-derived neurotrophic factor (BDNF) and neuropeptides. Here, we analyzed CPE and SgIII in the cerebral cortex of AD patients and transgenic mice. In the normal human cortex, a preferential location in dendrites and perikarya was observed for CPE, whereas SgIII was mainly associated with axons and terminal-like buttons. Interestingly, SgIII and CPE were consistently detected in astroglial cell bodies and thin processes. In AD cortices, a strong wide accumulation of both sorting receptors was detected in dystrophic neurites surrounding amyloid plaques. Occasionally, increased levels of SgIII were also observed in plaque associate-reactive astrocytes. Of note, the main alterations detected for CPE and SgIII in AD patients were faithfully recapitulated by APPswe/PS1dE9 mice. These results implicate for the first time the sorting receptors for regulated secretion in amyloid beta-associated neural degeneration. Because CPE and SgIII are essential in the process and targeting of neuropeptides and neurotrophins, their participation in the pathological progression of AD may be suggested. CI - (c) 2012 The Authors; Brain Pathology (c) 2012 International Society of Neuropathology. FAU - Pla, Virginia AU - Pla V AD - Department of Cell Biology, University of Barcelona, Barcelona, Spain. FAU - Paco, Sonia AU - Paco S FAU - Ghezali, Gregory AU - Ghezali G FAU - Ciria, Victor AU - Ciria V FAU - Pozas, Esther AU - Pozas E FAU - Ferrer, Isidro AU - Ferrer I FAU - Aguado, Fernando AU - Aguado F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121101 PL - Switzerland TA - Brain Pathol JT - Brain pathology (Zurich, Switzerland) JID - 9216781 RN - 0 (Amyloid beta-Peptides) RN - 0 (Chromogranins) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (secretogranin III) RN - EC 3.4.17.10 (Carboxypeptidase H) SB - IM MH - Aged MH - Aged, 80 and over MH - Alzheimer Disease/*metabolism/*pathology MH - Amyloid beta-Peptides/*genetics/*metabolism MH - Animals MH - Astrocytes/metabolism/pathology MH - Blotting, Western MH - Carboxypeptidase H/*genetics/*metabolism MH - Cerebral Cortex/metabolism/pathology MH - Chromogranins/*genetics/*metabolism MH - Female MH - Glial Fibrillary Acidic Protein/metabolism MH - Humans MH - Immunohistochemistry MH - Male MH - Mice MH - Mice, Transgenic MH - Microscopy, Electron MH - Middle Aged MH - Nerve Degeneration/*metabolism/*pathology MH - Plaque, Amyloid/metabolism/pathology PMC - PMC8028878 EDAT- 2012/09/25 06:00 MHDA- 2013/10/29 06:00 PMCR- 2012/11/01 CRDT- 2012/09/25 06:00 PHST- 2012/05/22 00:00 [received] PHST- 2012/09/12 00:00 [accepted] PHST- 2012/09/25 06:00 [entrez] PHST- 2012/09/25 06:00 [pubmed] PHST- 2013/10/29 06:00 [medline] PHST- 2012/11/01 00:00 [pmc-release] AID - BPA644 [pii] AID - 10.1111/j.1750-3639.2012.00644.x [doi] PST - ppublish SO - Brain Pathol. 2013 May;23(3):274-84. doi: 10.1111/j.1750-3639.2012.00644.x. Epub 2012 Nov 1.