γ-Radiation induces long-term dose-related proteomic and phosphorylated-tau species changes in non-human primate hippocampus.
8 affiliations
- 1DoW/USU Brain Tissue Repository & Neuropathology Program, Uniformed Services University (USU), Bethesda, MD USA.
- 2Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD USA.
- 3The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc, Bethesda, MD USA.
- 4Department of Pathology, Section on Comparative Medicine,, Wake Forest University, School of Medicine, Winston-Salem, NC USA.
- 5Mass Spectrometry and Proteomics, Department of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore, MD USA.
- 6Genetic Resources Core Facility (GRCF), School of Medicine, Johns Hopkins University, Baltimore, MD USA.
- 7Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD USA.
- 8Neuroscience Program, Department of Anatomy, Physiology & Genetics, Uniformed Services University (USU), Bethesda, MD USA.
Abstract
Long-term neurological consequences of acute total-body γ-radiation are poorly understood. Here we investigated the persistency of molecular changes in non-human primates (NHPs) 5+ years after single exposure to ~4 Gy or ~8 Gy total body irradiation dose. MS-based proteomic analyses were performed on samples of micro-dissected hippocampus from brains of irradiated/control NHPs. We used STRING and DAVID analyses to expand interpretation of proteomic data. Proteomic findings were further assessed using Western blot and digital-PCR. Proteomic analysis of the hippocampus revealed profound, dose-dependent molecular changes. ~4 Gy primarily impacted synaptic plasticity, while ~8 Gy affected catabolism, vascular development, and inflammation. Apelin receptor (APLNR) was the only protein consistently lowered at both radiation doses, suggesting it may be a key biomarker for radiation-induced brain injury. Significantly, while most proteins linked to neurodegeneration were unchanged, Tau (MAPT) protein levels increased at ~8 Gy, and some animals developed Tau-positive lesions resembling neurofibrillary tangles. Moreover, we found complex, dose-specific alterations in phosphorylated forms of other key proteins (alpha-synuclein, TDP-43). Overall, these findings show that different radiation doses induce distinct, persistent molecular changes in NHP hippocampus. This work highlights dysregulation of proteins usually associated with neurodegeneration (i.e., Tau and synaptic proteins) as a major long-term consequence of radiation, providing new insights into the molecular shift that accompany post-exposure high-dose radiation and likely a possible cause of post-exposure cognitive deficits.
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BibTeX
@article{hatch2026γradiation,
title = {{γ-Radiation induces long-term dose-related proteomic and phosphorylated-tau species changes in non-human primate hippocampus.}},
author = {Kathleen Hatch and Erin K Murphy and John D Olson and Robert N Cole and Robert N O'Meally and Roxann G Ingersoll and Daniel P Perl and George W Schaaf and J Mark Cline and Diego Iacono},
journal = {NPJ dementia},
year = {2026},
month = oct,
doi = {10.1038/s44400-026-00149-w},
url = {https://europepmc.org/article/MED/42920473},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - γ-Radiation induces long-term dose-related proteomic and phosphorylated-tau species changes in non-human primate hippocampus.
AU - Kathleen Hatch
AU - Erin K Murphy
AU - John D Olson
AU - Robert N Cole
AU - Robert N O'Meally
AU - Roxann G Ingersoll
AU - Daniel P Perl
AU - George W Schaaf
AU - J Mark Cline
AU - Diego Iacono
PY - 2026
DA - 2026/10/22
JO - NPJ dementia
DO - 10.1038/s44400-026-00149-w
UR - https://europepmc.org/article/MED/42920473
AB - Long-term neurological consequences of acute total-body γ-radiation are poorly understood. Here we investigated the persistency of molecular changes in non-human primates (NHPs) 5+ years after single exposure to ~4 Gy or ~8 Gy total body irradiation dose. MS-based proteomic analyses were performed on samples of micro-dissected hippocampus from brains of irradiated/control NHPs. We used STRING and DAVID analyses to expand interpretation of proteomic data. Proteomic findings were further assessed using Western blot and digital-PCR. Proteomic analysis of the hippocampus revealed profound, dose-dependent molecular changes. ~4 Gy primarily impacted synaptic plasticity, while ~8 Gy affected catabolism, vascular development, and inflammation. Apelin receptor (APLNR) was the only protein consistently lowered at both radiation doses, suggesting it may be a key biomarker for radiation-induced brain injury. Significantly, while most proteins linked to neurodegeneration were unchanged, Tau (MAPT) protein levels increased at ~8 Gy, and some animals developed Tau-positive lesions resembling neurofibrillary tangles. Moreover, we found complex, dose-specific alterations in phosphorylated forms of other key proteins (alpha-synuclein, TDP-43). Overall, these findings show that different radiation doses induce distinct, persistent molecular changes in NHP hippocampus. This work highlights dysregulation of proteins usually associated with neurodegeneration (i.e., Tau and synaptic proteins) as a major long-term consequence of radiation, providing new insights into the molecular shift that accompany post-exposure high-dose radiation and likely a possible cause of post-exposure cognitive deficits.
SN - 3005-1940
ER -