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Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo

Nature neuroscience, 2019-01, Vol.22 (1), p.57-64 [Peer Reviewed Journal]

Copyright Nature Publishing Group Jan 2019 ;ISSN: 1097-6256 ;EISSN: 1546-1726 ;DOI: 10.1038/s41593-018-0289-8 ;PMID: 30559471

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Title:
Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
Author: Busche, Marc Aurel ; Wegmann, Susanne ; Dujardin, Simon ; Commins, Caitlin ; Schiantarelli, Julia ; Klickstein, Naomi ; Kamath, Tarun V ; Carlson, George A ; Nelken, Israel ; Hyman, Bradley T
Subjects: Alzheimer Disease - genetics ; Alzheimer Disease - metabolism ; Alzheimer Disease - pathology ; Amyloid ; Animal models ; Animals ; Brain - metabolism ; Brain - pathology ; Calcium imaging ; Calcium ions ; Circuits ; Coexistence ; Cognitive ability ; Cortex ; Disease Models, Animal ; Functional morphology ; Gene expression ; Hyperactivity ; Mice ; Nerve Net - metabolism ; Nerve Net - pathology ; Neural networks ; Neurofibrillary tangles ; Neurofibrillary Tangles - metabolism ; Neurofibrillary Tangles - pathology ; Neurons ; Neurons - metabolism ; Neurons - pathology ; Plaque, Amyloid - genetics ; Plaque, Amyloid - metabolism ; Plaques ; Synergism ; Tau protein ; tau Proteins - genetics ; tau Proteins - metabolism
Is Part Of: Nature neuroscience, 2019-01, Vol.22 (1), p.57-64
Description: 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 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.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1097-6256
EISSN: 1546-1726
DOI: 10.1038/s41593-018-0289-8
PMID: 30559471
Source: ProQuest One Psychology
MEDLINE
ProQuest Central

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Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo

Copyright Nature Publishing Group Jan 2019 ;ISSN: 1097-6256 ;EISSN: 1546-1726 ;DOI: 10.1038/s41593-018-0289-8 ;PMID: 30559471

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