In Alzheimer's disease, which neurotransmitter system is preferentially affected?

• A. Acetylcholine deficiency
• B. Serotonin deficiency
• C. Norepinephrine excess
• D. Dopamine excess

Answer: (A)

Alzheimer's disease preferentially reduces acetylcholine signaling because the basal forebrain cholinergic neurons that project to the hippocampus and cortex degenerate. Acetylcholine is crucial for encoding and consolidating memories, so loss of cholinergic input to memory-related regions leads to the prominent memory impairment seen in this disease. This is why acetylcholinesterase inhibitors—which raise acetylcholine levels—can provide modest cognitive improvement. Other neurotransmitter systems can be affected later or to a lesser extent, but the earliest and most characteristic change is a deficiency of acetylcholine.