Molecular Changes Underlying Reduced Pineal Melatonin Levels in Alzheimer Disease: Alterations in Preclinical and Clinical Stages

Dec 13, 2003The Journal of clinical endocrinology and metabolism

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

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Abstract

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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