Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain
| Autor: | Kimberly M. Alonge, Randy Woltjer, Bao Anh Phan, William A. Banks, C. Dirk Keene, Vy Nguyen, Chelsea L. Faber, Michael W. Schwartz, Caitlin S. Latimer, Naly Setthavongsack, Kendra L. Francis, Aric F. Logsdon, Nicole E. Richardson, Jarrad M. Scarlett, Shannon J. Hu |
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| Rok vydání: | 2021 |
| Předmět: |
Glycan
Epidemiology Article Extracellular matrix Cellular and Molecular Neuroscience chemistry.chemical_compound Sulfation Developmental Neuroscience Alzheimer Disease Tandem Mass Spectrometry medicine Humans Dementia Chondroitin biology business.industry Health Policy Perineuronal net Brain Cognition medicine.disease Extracellular Matrix Psychiatry and Mental health chemistry biology.protein Neurology (clinical) Geriatrics and Gerontology business Neuroscience Neurocognitive Chromatography Liquid |
| Zdroj: | Alzheimers Dement |
| ISSN: | 1552-5279 1552-5260 |
| Popis: | The extracellular matrix (ECM) of the brain is comprised of 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 are reported in patients with neurocognitive and neuropsychiatric disorders including Alzheimer’s disease (AD). Using liquid hromatography 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. |
| Databáze: | OpenAIRE |
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