Neuroimmune proteins can differentiate between tauopathies.

Autor: Cherry JD; VA Boston Healthcare System, 150 S. Huntington Ave., Boston, MA, 02130, USA. Jdcherry@bu.edu.; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA , USA. Jdcherry@bu.edu.; Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA. Jdcherry@bu.edu., Baucom ZH; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Eppich KG; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Kirsch D; VA Boston Healthcare System, 150 S. Huntington Ave., Boston, MA, 02130, USA.; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA , USA.; Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA., Dixon ER; VA Boston Healthcare System, 150 S. Huntington Ave., Boston, MA, 02130, USA.; Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA., Tripodis Y; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Bieniek KF; Department of Pathology, UT Health San Antonio, San Antonio, TX, USA.; Gleen Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA., Farrell K; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Artificial Intelligence, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Neuropathology Brain Bank and Research CoRE, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Whitney K; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Artificial Intelligence, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Neuropathology Brain Bank and Research CoRE, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Uretsky M; Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA., Crary JF; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Artificial Intelligence, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Neuropathology Brain Bank and Research CoRE, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Dickson D; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA., McKee AC; VA Boston Healthcare System, 150 S. Huntington Ave., Boston, MA, 02130, USA.; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA , USA.; Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2022 Nov 19; Vol. 19 (1), pp. 278. Date of Electronic Publication: 2022 Nov 19.
DOI: 10.1186/s12974-022-02640-6
Abstrakt: Background: Tauopathies are a group of neurodegenerative diseases where there is pathologic accumulation of hyperphosphorylated tau protein (ptau). The most common tauopathy is Alzheimer's disease (AD), but chronic traumatic encephalopathy (CTE), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and argyrophilic grain disease (AGD) are significant health risks as well. Currently, it is unclear what specific molecular factors might drive each distinct disease and represent therapeutic targets. Additionally, there is a lack of biomarkers that can differentiate each disease in life. Recent work has suggested that neuroinflammatory changes might be specific among distinct diseases and offers a novel resource for mechanistic targets and biomarker candidates.
Methods: To better examine each tauopathy, a 71 immune-related protein multiplex ELISA panel was utilized to analyze anterior cingulate grey matter from 127 individuals neuropathologically diagnosed with AD, CTE, PSP, CBD, and AGD. A partial least square regression analysis was carried out to perform unbiased clustering and identify proteins that are distinctly correlated with each tauopathy correcting for age and gender. Receiver operator characteristic and binary logistic regression analyses were then used to examine the ability of each candidate protein to distinguish diseases. Validation in postmortem cerebrospinal fluid (CSF) from 15 AD and 14 CTE cases was performed to determine if candidate proteins could act as possible novel biomarkers.
Results: Five clusters of immune proteins were identified and compared to each tauopathy to determine if clusters were specific to distinct disease. Each cluster was found to correlate with either CTE, AD, PSP, CBD, or AGD. When examining which proteins were the strongest driver of each cluster, it was observed the most distinctive protein for CTE was CCL21, AD was FLT3L, and PSP was IL13. Individual proteins that were specific to CBD and AGD were not observed. CCL21 was observed to be elevated in CTE CSF compared to AD cases (p = 0.02), further validating the use as possible biomarkers. Sub-analyses for male only cases confirmed the results were not skewed by gender differences.
Conclusions: Overall, these results highlight that different neuroinflammatory responses might underlie unique mechanisms in related neurodegenerative pathologies. Additionally, the use of distinct neuroinflammatory signatures could help differentiate between tauopathies and act as novel biomarker candidate to increase specificity for in-life diagnoses.
(© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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