Molecular changes linked to lower nighttime melatonin levels in early and advanced Alzheimer’s disease

Melatonin levels in the cerebrospinal fluid decrease during the progression of Alzheimer's disease, particularly in early stages.

• A disturbed sleep-wake rhythm is common in Alzheimer's disease patients and is associated with lower melatonin levels.
• Cerebrospinal fluid melatonin levels correlate highly with melatonin levels in the pineal glands.
• The circadian melatonin rhythm is lost in both preclinical Alzheimer's and definite Alzheimer's patients due to decreased nocturnal melatonin levels.
• The circadian rhythm of beta(1)-adrenergic receptor mRNA is also absent in both patient groups.
• Serotonin, a precursor to melatonin, is progressively depleted during Alzheimer's disease, indicated by increased levels of monoamine oxidase A mRNA and activity.

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