The Accumulation of Tau-Immunoreactive Hippocampal Granules and Corpora Amylacea Implicates Reactive Glia in Tau Pathogenesis during Aging
| Autor: | Rick B. Meeker, Heba Al Housseiny, Connor M. Wander, Yen-Yu Ian Shih, Sheng Song, Jui-Heng Tseng, Aditi Ajit, Juan Song, David J. Irwin, Todd J. Cohen, Dalton S. Tart, Rebecca Lobrovich |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Tau protein 02 engineering and technology Molecular neuroscience Biology Hippocampal formation Article Pathogenesis 03 medical and health sciences mental disorders medicine lcsh:Science Neuroinflammation Multidisciplinary Microglia Human brain 021001 nanoscience & nanotechnology Cell biology 030104 developmental biology medicine.anatomical_structure Cellular Neuroscience biology.protein lcsh:Q Molecular Neuroscience 0210 nano-technology Corpora amylacea Neuroscience |
| Zdroj: | iScience iScience, Vol 23, Iss 7, Pp 101255-(2020) |
| ISSN: | 2589-0042 |
| Popis: | Summary The microtubule-associated tau protein forms pathological inclusions that accumulate in an age-dependent manner in tauopathies including Alzheimer's disease (AD). Since age is the major risk factor for AD, we examined endogenous tau species that evolve during aging in physiological and diseased conditions. In aged mouse brain, we found tau-immunoreactive clusters embedded within structures that are reminiscent of periodic acid-Schiff (PAS) granules. We showed that PAS granules harbor distinct tau species that are more prominent in 3xTg-AD mice. Epitope profiling revealed hypo-phosphorylated rather than hyper-phosphorylated tau commonly observed in tauopathies. High-resolution imaging and 3D reconstruction suggest a link between tau clusters, reactive astrocytes, and microglia, indicating that early tau accumulation may promote neuroinflammation during aging. Using postmortem human brain, we identified tau as a component of corpora amylacea (CA), age-related structures that are functionally analogous to PAS granules. Overall, our study supports neuroimmune dysfunction as a precipitating event in tau pathogenesis. Graphical Abstract Highlights • Tau is present in mouse hippocampal granules and human corpora amylacea • Tau accumulates with age in hippocampal granules and is accelerated in 3xTg-AD mice • Tau immunoreactive corpora amylacea are present in Alzheimer's disease brain • Age-related tau deposits are associated with reactive astrocytes Neuroscience; Molecular Neuroscience; Cellular Neuroscience |
| Databáze: | OpenAIRE |
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