Abstract
Parkinsonism–dementia complex of Guam (Guam PDC) is a neurodegenerative disease with parkinsonism and early onset Alzheimer-like dementia. Guam PDC belongs to the family of neurodegenerative disorders, known as tauopathies, which are histopathologically characterized by abnormal deposition of microtubule-associated protein tau. While changes in the blood–brain barrier (BBB) in Alzheimer’s disease are increasingly recognized, dysfunction of BBB in Guam PDC has not been extensively studied. In this study, we characterized cerebrovascular changes in the patients with Guam PDC. The brain tissue from ten post-mortem Guam PDC patients and six non-demented controls were assessed for structural and functional changes in BBB. Entorhinal cortex sections were immunostained for the markers of brain endothelial cells (claudin-5, occludin, and collagen IV) and inflammation (VCAM-1, ICAM-1, P-Selectin, and E-Selectin). The ultrastructure of brain capillaries was investigated by confocal microscopy and morphological changes and intensity alterations were evaluated. We found a significant decrease of tight junction proteins and the upregulation of adhesion molecules that correlated with the presence of neurofibrillary tangles. In addition, we showed the presence of CD3+-positive cells in the brain areas affected by pathological lesions. Our findings indicate that pathological lesions in Guam PDC are associated with inflammatory changes of brain capillaries and could mediate transmigration of cells to the brain parenchyma.
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Abbreviations
- AD:
-
Alzheimer’s disease
- BBB:
-
Blood–brain barrier
- NFT:
-
Neurofibrillary tangles
- Guam PDC:
-
Parkinsonism–dementia complex of Guam
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Acknowledgements
We thank the Chamorro families and Guamanian patients who made this research possible. We also thank the Binghamton University Biospecimen Archive Facility (Binghamton NY, USA) for providing the brain tissue and Axon Neuroscience R&D Services SE for DC11 antibody. This work was supported by Grants APVV-14-0547 and VEGA 2/0088/18, and structural funds 26240220008 and 26240220046.
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PM and AK designed the study, acquired, analyzed, and interpreted the histologic data. RG contributed to the study design, tissue, and data acquisition and analysis. PM, AK, and RG drafted the manuscript. All authors read and approved the final manuscript.
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Majerova, P., Garruto, R.M. & Kovac, A. Cerebrovascular inflammation is associated with tau pathology in Guam parkinsonism dementia. J Neural Transm 125, 1013–1025 (2018). https://doi.org/10.1007/s00702-018-1883-3
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DOI: https://doi.org/10.1007/s00702-018-1883-3