@article{92f797abbbce4b4aa0e1dd08810a8b6f,
title = "Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain",
abstract = "The extracellular matrix (ECM) of the brain comprises unique glycan “sulfation codes” that influence neurological function. Perineuronal nets (PNNs) are chondroitin sulfate-glycosaminoglycan (CS-GAG) containing matrices that enmesh neural networks involved in memory and cognition, and loss of PNN matrices is reported in patients with neurocognitive and neuropsychiatric disorders including Alzheimer's disease (AD). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), we show that patients with a clinical diagnosis of AD-related dementia undergo a re-coding of their PNN-associated CS-GAGs that correlates to Braak stage progression, hyperphosphorylated tau (p-tau) accumulation, and cognitive impairment. As these CS-GAG sulfation changes are detectable prior to the regional onset of classical AD pathology, they may contribute to the initiation and/or progression of the underlying degenerative processes and implicate the brain matrix sulfation code as a key player in the development of AD clinicopathology.",
keywords = "Alzheimer's disease, brain, chondroitin sulfates, cognition, extracellular matrix, glycosaminoglycans, mass spectrometry, perineuronal nets, tau",
author = "Logsdon, {Aric F.} and Francis, {Kendra L.} and Richardson, {Nicole E.} and Hu, {Shannon J.} and Faber, {Chelsea L.} and Phan, {Bao Anh} and Vy Nguyen and Naly Setthavongsack and Banks, {William A.} and Woltjer, {Randy L.} and Keene, {C. Dirk} and Latimer, {Caitlin S.} and Schwartz, {Michael W.} and Scarlett, {Jarrad M.} and Alonge, {Kimberly M.}",
note = "Funding Information: The authors are grateful to the subjects who donated their brains for this research and their loved ones; for the expert technical assistance of Lisa Keene, Kim Howard, Katelyn Kern, and Amanda Keen; and administrative support of Aimee Schantz (University of Washington, BioRepository and Integrated Neuropathology [BRaIN] Laboratory). Biostatistical support by Sarah E. Holte was provided by the University of Washington Nutrition and Obesity Research Center (P30 DK035816) from the National Institute of Diabetes and Digestive and Kidney Disease (NIH‐NIDDK). Histochemical work was supported by the University of Washington Medicine Diabetes Institute (UWMDI) and mass spectrometry work was supported by University of Washington School of Pharmacy Mass Spectrometry Center. This work was also supported by NIH‐NIDDK grants DK122662 (KMA), DK101997 and DK‐720269 (MWS), DK114474 (JMS), DK007742 (KLF), and DK007247 (NER and CLF); and the National Institute of Aging (NIH‐NIA) grants AG066509 (KMA), AG065426 (CSL), P30 AG066509 (UW Alzheimer's Disease Research Center), U01 AG006781 (Adult Changes in Thought study), and P50 AG066518 (Oregon Alzheimer's Disease Research Center). Additional funding provided by the Nancy and Buster Alvord Endowment (CDK), UW Royalty Research Fund (RRF A139339) to JMS, ITHS Young Investigator Catalyst Award to KMA (BR 013035), and funding to KMA and JMS by the UW Diabetes Research Center (DRC) NIH‐NIDDK sponsored grant DK017047. Some figures were created using BioRender.com. Funding Information: The authors are grateful to the subjects who donated their brains for this research and their loved ones; for the expert technical assistance of Lisa Keene, Kim Howard, Katelyn Kern, and Amanda Keen; and administrative support of Aimee Schantz (University of Washington, BioRepository and Integrated Neuropathology [BRaIN] Laboratory). Biostatistical support by Sarah E. Holte was provided by the University of Washington Nutrition and Obesity Research Center (P30 DK035816) from the National Institute of Diabetes and Digestive and Kidney Disease (NIH-NIDDK). Histochemical work was supported by the University of Washington Medicine Diabetes Institute (UWMDI) and mass spectrometry work was supported by University of Washington School of Pharmacy Mass Spectrometry Center. This work was also supported by NIH-NIDDK grants DK122662 (KMA), DK101997 and DK-720269 (MWS), DK114474 (JMS), DK007742 (KLF), and DK007247 (NER and CLF); and the National Institute of Aging (NIH-NIA) grants AG066509 (KMA), AG065426 (CSL), P30 AG066509 (UW Alzheimer's Disease Research Center), U01 AG006781 (Adult Changes in Thought study), and P50 AG066518 (Oregon Alzheimer's Disease Research Center). Additional funding provided by the Nancy and Buster Alvord Endowment (CDK), UW Royalty Research Fund (RRF A139339) to JMS, ITHS Young Investigator Catalyst Award to KMA (BR 013035), and funding to KMA and JMS by the UW Diabetes Research Center (DRC) NIH-NIDDK sponsored grant DK017047. Some figures were created using BioRender.com. Funding Information: KMA reports NIH support and a travel award from the University of Washington; AFL reports NIH support, a travel award from Brain & Brain PET, a provisional patent for CTE treatment, and is a Board Member for CTEC, LLC (Prophos Neurosciences); NER reports NIH funding, UW‐Madison Student Research Grant, a travel award to Central Society for Clinical and Translational Research, a travel award for American Aging Association, and holds a provisional patent for Compositions and Methods for Restoring Metabolic Health; CLF reports NIH support; WAB reports NIH support, consulting fees for the Federal Trade Commission, and a leadership role for Siber (nonprofit); CDK reports NIH and DoD support, a travel award for a NIH grant review session; CSL reports NIH support and a relationship with the National Academy of Neuropsychology; MWS reports NIH support, a honoraria for the Albert Einstein School of Medicine, a honoraria for the University of Toronto, a honoraria for the University of Colorado, and a Research Agreement with Novo Nordisk; JSA reports NIH support, a UW Royalty Research Funds award, a travel award to Helmholtz Diabetes Conference, a travel award to Symposium on Hormones and Cell Regulation, a travel award to Japan Diabetes Society, and a travel award to Japan Insulin Study Group; RLW reports NIH support; KLF reports NIH support ; BAP, VN, NS, and SJH report no disclosures. Publisher Copyright: {\textcopyright} 2021 the Alzheimer's Association.",
year = "2022",
month = may,
doi = "10.1002/alz.12451",
language = "English (US)",
volume = "18",
pages = "942--954",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "5",
}