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Published on: September 20, 2018
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Clinical Manifestations.
1University of Southern California, Los Angeles, CA, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
Summary
Researchers identified the septum
Area of Science:
- Neuroscience
- Alzheimer's Disease Research
Background:
- Apathy is a common Alzheimer's disease (AD) symptom, impacting patients and caregivers.
- Neuronal mechanisms of apathy in AD are poorly understood.
- The septum, involved in motivation, shows early AD pathology, suggesting its role in apathy.
Purpose of the Study:
- Investigate the septum's role in Alzheimer's disease-related apathy.
- Determine the function of septal GABAergic neurons in apathy phenotypes.
Main Methods:
- Assessed apathy-like behaviors in 5xFAD mice across multiple ages.
- Quantified social interaction and motivation using automated behavioral analysis.
- Performed electrophysiological recordings and optogenetic/chemogenetic manipulations of septal neurons.
Main Results:
- 5xFAD mice exhibited early-onset apathy-like behaviors, including reduced social engagement.
- Altered septal neuronal activity correlated with apathy phenotypes.
- Functional impairments in septal GABAergic neurons were identified and targeted for rescue.
Conclusions:
- The septum is a critical brain region involved in Alzheimer's disease apathy.
- Septal dysfunction contributes to apathy in AD.
- Targeting septal pathways offers potential therapeutic strategies for AD apathy.
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