Acetylcholinergic neurotransmission and the β-amyloid cascade: implications for Alzheimer’s disease

Abstract

Alzheimer’s disease is characterized by both decreases in acetylcholinergic neurotransmission and increases in β-amyloid accumulation. Currently, available clinical psychopharmacologic treatment is focused on increasing acetylcholinergic neurotransmission, whereas no clinical treatments to directly reduce β-amyloid accumulation are available. Cholinesterase inhibitors improve cognition, certain neuropsychiatric symptoms and functional impairment in patients with mild-to-moderate Alzheimer’s disease, and it is believed that this is mainly symptomatic treatment. However, this review discusses various levels of interaction between acetylcholinergic neurotransmission and the β-amyloid cascade, which suggest that some specific acetylcholinergic treatments may reduce β-amyloid accumulation, and therefore may slow disease progression over the long term. Various suggestions are made on how such potential disease-modifying effects could be studied in the future.

Keywords::

• acetylcholinesterase
• Alzheimer’s disease,
• amyloid
• amyloid-β protein
• butyrylcholinesterase
• muscarinic receptor
• nicotinic receptor
• senile plaques