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Cholinergic deficiency in Alzheimer's disease. Pathogenic model
1Department of Psychiatry, Neurology, and Gerontology, University of Southern California School of Medicine, Los Angeles, USA.
Summary
Alzheimer's disease (AD) involves neurodegeneration in specific brain regions, not the whole brain. Targeting neurotransmitter systems offers promising therapeutic interventions for AD.
Area of Science:
- Neuroscience
- Neurology
- Pharmacology
Background:
- Genetic vulnerability is increasingly recognized in Alzheimer's disease (AD), though most cases are not purely genetic.
- Early neurodegeneration in AD affects specific cholinergically innervated regions, suggesting a corticolimbic system disorder.
Purpose of the Study:
- To conceptualize Alzheimer's disease (AD) as a corticolimbic system neurodegenerative disorder.
- To explore therapeutic intervention strategies targeting neurodegeneration and clinical signs in AD.
Main Methods:
- Conceptualizing AD based on early neurodegenerative patterns in specific brain regions (entorhinal cortex, hippocampus, amygdala).
- Reviewing existing and potential therapeutic approaches including risk factor modulation, amyloid and tau targeting, anti-inflammatory and antioxidant strategies, and cholinergic enhancement.
Main Results:
- Antioxidants like vitamin E and selegiline have shown potential in prolonging time to adverse outcomes.
- Anti-inflammatory use may reduce AD risk, and cholinesterase inhibitors may delay nursing home placement.
Conclusions:
- AD can be viewed as a neurodegenerative disorder of the corticolimbic system.
- Modulating risk factors, pathological proteins, inflammatory processes, and enhancing cholinergic function are viable therapeutic strategies.
- Neurotransmitter system-focused approaches represent immediately accessible targets for AD intervention.