Alzheimer's brain inoculation in Aβ-plaque bearing mice: synaptic loss is linked to tau seeding and low microglial activity
2021
Alzheimer's disease (AD) is characterized by synaptic alterations that lead to cognitive impairments and by a number of lesions including extracellular amyloid-{beta} (A{beta}) plaques, intracellular tau accumulation and neuroinflammation. The contribution of these lesions to synaptic alterations is still debated. Through the intracerebral injection of human AD brain extracts into an A{beta} plaque-bearing mouse model that does not overexpress tau we recapitulated all these AD lesions. In particular neuritic plaques, AD-like neurofibrillary tangles and neuropil threads, that spread through the brain, were identified and characterized. Interestingly neuritic plaques but not other tau-positive lesions were observed in control-inoculated animals as well as in non-inoculated amyloid-bearing mice, suggesting that these lesions do not require exogeneous tau to be initiated. Inoculation of different human AD brain extracts to mice led to lesional heterogeneity and to enhanced synaptic loss and cognitive impairments. Relationships between synaptic alterations or cognitive impairments and AD pathology were evaluated by exploiting the induced lesional heterogeneity. Synaptic loss and cognitive deficits were associated with the severity of tau lesions and to lower microglial load, but not to amyloid load. Our results outline that new mouse models of AD bearing both A{beta} plaques and tau lesions, and based on AD brain extracts inoculation, allow to investigate AD neurodegenerative processes. They highlight the contribution of tau to synaptic impairments in a model that does not rely on genetic manipulation of tau protein and indicate that microglial activity may protect against synaptic loss.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
45
References
1
Citations
NaN
KQI