Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
| Autor: | Bradley T. Hyman, Naomi Klickstein, Marc Aurel Busche, George A. Carlson, Tarun V. Kamath, Julia Schiantarelli, Israel Nelken, Susanne Wegmann, Simon Dujardin, Caitlin Commins |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetically modified mouse genetics [Plaque Amyloid] pathology [Nerve Net] genetics [Alzheimer Disease] Plaque Amyloid tau Proteins Article 03 medical and health sciences pathology [Alzheimer Disease] Mice 0302 clinical medicine In vivo pathology [Brain] Alzheimer Disease ddc:570 Gene expression mental disorders Biological neural network medicine Gene silencing pathology [Neurons] Animals Cognitive decline metabolism [Nerve Net] Neurons Neocortex Chemistry General Neuroscience Brain Neurofibrillary Tangles Entorhinal cortex metabolism [Plaque Amyloid] metabolism [tau Proteins] genetics [tau Proteins] Disease Models Animal 030104 developmental biology medicine.anatomical_structure metabolism [Neurofibrillary Tangles] metabolism [Brain] metabolism [Neurons] pathology [Neurofibrillary Tangles] Nerve Net Neuroscience 030217 neurology & neurosurgery metabolism [Alzheimer Disease] |
| Zdroj: | Nature reviews / Neuroscience 22(1), 57-64 (2018). doi:10.1038/s41593-018-0289-8 |
| ISSN: | 1546-1726 |
| DOI: | 10.1038/s41593-018-0289-8 |
| Popis: | The coexistence of amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the neocortex is linked to neural system failure and cognitive decline in Alzheimer’s disease. However, the underlying neuronal mechanisms are unknown. By employing in vivo two-photon Ca(2+) imaging of layer 2/3 cortical neurons in mice expressing human Aβ and tau, we reveal a dramatic tau-dependent suppression of activity and silencing of many neurons, which dominates over Aβ-dependent neuronal hyperactivity. We show that neurofibrillary tangles are neither sufficient nor required for the silencing, which instead is dependent on soluble tau. Surprisingly, although rapidly effective in tau mice, suppression of tau gene expression was much less effective in rescuing neuronal impairments in mice containing both Aβ and tau. Together, our results reveal how Aβ and tau synergize to impair the functional integrity of neural circuits in vivo and suggest a possible cellular explanation contributing to disappointing results from anti-Aβ therapeutic trials. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink