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• W4292184383 abstract "Abstract Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaques i.e. tau aggregates within neurites surrounding Aβ deposits. The cascade of events linking these lesions and synaptic or memory impairments are still debated. Intracerebral infusion of human AD brain extracts in Aβ plaque-bearing mice that do not overexpress pathological tau proteins induces tau pathologies following heterotopic seeding of mouse tau protein. There is however little information regarding the downstream events including synaptic or cognitive repercussions of tau pathology induction in these models. In the present study, human AD brain extracts (AD be ) and control-brain extracts (Ctrl be ) were infused into the hippocampus of Aβ plaque-bearing APP swe /PS1 dE9 mice. Memory, synaptic density, as well as Aβ plaque and tau aggregate loads, microgliosis, astrogliosis at the inoculation site and in connected regions (perirhinal/entorhinal cortex) were evaluated 4 and 8 months post-inoculation. AD be inoculation produced the following effects: (i) memory deficit; (ii) increased Aβ plaque deposition in proximity to the inoculation site; (iii) tau pathology induction; (iv) appearance of neuropil threads and neurofibrillary tangles next to the inoculation site with a spreading to connected regions. Neuritic plaque pathology was detected in both AD be - and Ctrl be -inoculated animals but AD be inoculation increased the severity close to and at distance of the inoculation site. (v) Finally, AD be inoculation reduced synaptic density in the vicinity to the inoculation site and in connected regions as the perirhinal/entorhinal cortex. Synaptic impairments were correlated with increased severity of neuritic plaques but not to other tau lesions or Aβ lesions, suggesting that neuritic plaques are a culprit for synaptic loss. Synaptic density was also associated with microglial load. Graphical abstract" @default.
• W4292184383 created "2022-08-18" @default.
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• W4292184383 date "2022-08-16" @default.
• W4292184383 modified "2023-10-16" @default.
• W4292184383 title "Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice" @default.
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• W4292184383 doi "https://doi.org/10.1186/s40478-022-01410-y" @default.
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