Localized amyloid-β oligomers in the lateral entorhinal cortex drives olfactory dysfunction through aberrant neuronal...

Area of Science:

• Neuroscience
• Pathology
• Olfactory system research

Background:

• Olfactory dysfunction is a common early symptom of Alzheimer's disease (AD).
• The lateral entorhinal cortex (LEC) is an early site of AD pathology and crucial for olfaction.
• Direct causal links between LEC dysfunction and olfactory deficits in early AD are not well-established.

Purpose of the Study:

• To investigate the causal role of LEC dysfunction in early AD-related olfactory disorders.
• To explore the neural mechanisms by which LEC dysfunction contributes to olfactory impairment in AD.

Main Methods:

• Amyloid-beta (Aβ)_1-42 oligomers were injected into the LEC of mice to induce localized Aβ accumulation.
• Behavioral tests assessed odor detection and discrimination.
• In vivo recordings monitored neuronal activity and oscillations in the LEC.
• Synaptic structure and transmission were examined.

Main Results:

• Localized Aβ oligomers in the LEC significantly impaired odor detection and discrimination.
• Aβ oligomers induced hyperactivity in LEC neurons, increasing baseline and odor-evoked activity.
• Odor-evoked beta oscillations were enhanced, correlating with disrupted population-level odor decoding.
• Deficits in synaptic structure and impaired synaptic transmission were observed.

Conclusions:

• LEC dysfunction, induced by localized Aβ oligomers, directly causes olfactory deficits.
• Hyperactivity and altered network oscillations in the LEC are key neural mechanisms underlying AD-related olfactory impairment.
• These findings provide direct evidence for the LEC's involvement in early AD olfactory dysfunction.