Differences in Synaptic Dysfunction Between rTg4510 and APP/PS1 Mouse Models of Alzheimer's Disease

Area of Science:

• Neuroscience
• Genetics
• Pathology

Background:

• Genetically modified mice are crucial for studying Alzheimer's disease (AD) progression.
• Two common models, rTg4510 (mutant Tau) and APP/PS1 (mutant amyloid precursor protein/presenilin 1), exhibit hippocampal deficits.
• Comparative synaptic pathology analyses between these models are limited.

Purpose of the Study:

• To comparatively analyze synaptic transmission and plasticity deficits in rTg4510 and APP/PS1 mouse models of AD.
• To investigate early pathological differences in basal synaptic transmission (BST), paired-pulse facilitation (PPF), and long-term potentiation (LTP).

Main Methods:

• Extracellular field potential recordings in hippocampal slices.
• Assessment of basal synaptic transmission (BST), paired-pulse facilitation (PPF), and long-term potentiation (LTP).
• Analysis of fiber volley (FV) amplitude and field excitatory post-synaptic potential (fEPSP) slope.

Main Results:

• rTg4510 mice showed reduced presynaptic activation (FV) and synaptic transmission (fEPSP) at 6-7 months, with no BST deficit when normalized.
• APP/PS1 mice exhibited reduced fEPSP (BST deficit) at 8-10 months, with normal FV.
• Long-term potentiation (LTP) deficits were observed in older mice of both models, while PPF was impaired earlier in rTg4510 mice.

Conclusions:

• Synaptic transmission deficits manifest earlier in APP/PS1 mice than previously thought.
• Presynaptic and synaptic plasticity deficits emerge earlier in the rTg4510 Tau model.
• Distinct temporal profiles of synaptic pathology progression exist between Tau and amyloid mouse models of AD.