Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain

Aric F. Logsdon; Kendra L. Francis; Nicole E. Richardson; Shannon J. Hu; Chelsea L. Faber; Bao Anh Phan; Vy Nguyen; Naly Setthavongsack; William A. Banks; Randy L. Woltjer; C. Dirk Keene; Caitlin S. Latimer; Michael W. Schwartz; Jarrad M. Scarlett; Kimberly M. Alonge

doi:10.1002/alz.12451

Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain

Aric F. Logsdon, Kendra L. Francis, Nicole E. Richardson, Shannon J. Hu, Chelsea L. Faber, Bao Anh Phan, Vy Nguyen, Naly Setthavongsack, William A. Banks, Randy L. Woltjer, C. Dirk Keene, Caitlin S. Latimer, Michael W. Schwartz, Jarrad M. Scarlett, Kimberly M. Alonge

Pathology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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.

Original language	English (US)
Pages (from-to)	942-954
Number of pages	13
Journal	Alzheimer's and Dementia
Volume	18
Issue number	5
DOIs	https://doi.org/10.1002/alz.12451
State	Published - May 2022

Keywords

Alzheimer's disease
brain
chondroitin sulfates
cognition
extracellular matrix
glycosaminoglycans
mass spectrometry
perineuronal nets
tau

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1002/alz.12451

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Logsdon, A. F., Francis, K. L., Richardson, N. E., Hu, S. J., Faber, C. L., Phan, B. A., Nguyen, V., Setthavongsack, N., Banks, W. A., Woltjer, R. L., Keene, C. D., Latimer, C. S., Schwartz, M. W., Scarlett, J. M., & Alonge, K. M. (2022). Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain. Alzheimer's and Dementia, 18(5), 942-954. https://doi.org/10.1002/alz.12451

Logsdon, AF, Francis, KL, Richardson, NE, Hu, SJ, Faber, CL, Phan, BA, Nguyen, V, Setthavongsack, N, Banks, WA, Woltjer, RL, Keene, CD, Latimer, CS, Schwartz, MW, Scarlett, JM & Alonge, KM 2022, 'Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain', Alzheimer's and Dementia, vol. 18, no. 5, pp. 942-954. https://doi.org/10.1002/alz.12451

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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.}",

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doi = "10.1002/alz.12451",

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AU - Francis, Kendra L.

AU - Richardson, Nicole E.

AU - Hu, Shannon J.

AU - Faber, Chelsea L.

AU - Phan, Bao Anh

AU - Nguyen, Vy

AU - Setthavongsack, Naly

AU - Banks, William A.

AU - Woltjer, Randy L.

AU - Keene, C. Dirk

AU - Latimer, Caitlin S.

AU - Schwartz, Michael W.

AU - Scarlett, Jarrad M.

AU - Alonge, Kimberly M.

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AB - 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.

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Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain

Abstract

Keywords

ASJC Scopus subject areas

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