The human pineal gland and melatonin in aging and Alzheimer's disease

Feb 24, 2005Journal of pineal research

The human pineal gland and melatonin levels in aging and Alzheimer's disease

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Abstract

Melatonin production and rhythms may be disrupted as early as the first preclinical stages of Alzheimer's disease (neuropathological Braak stage I-II).

The pineal gland produces melatonin, regulated by the suprachiasmatic nucleus (SCN), which is synchronized to the 24-hour day by environmental light.
Melatonin is associated with the regulation of circadian rhythms and may act as an antioxidant and neuroprotector, particularly in aging and Alzheimer's disease.
Circadian disorders, including sleep-wake cycle disturbances, are linked to aging and are more pronounced in Alzheimer's disease.
Dysfunction in the sympathetic regulation of pineal melatonin synthesis by the SCN may contribute to changes in melatonin production during early stages of Alzheimer's disease.
Light therapy and melatonin supplementation could potentially reactivate the circadian system and alleviate clinical circadian disturbances.

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The pineal gland is a central structure in the circadian system which produces melatonin under the control of the central clock, the suprachiasmatic nucleus (SCN). The SCN and the output of the pineal gland, i.e. melatonin, are synchronized to the 24-hr day by environmental light, received by the retina and transmitted to the SCN via the retinohypothalamic tract. Melatonin not only plays an important role in the regulation of circadian rhythms, but also acts as antioxidant and neuroprotector that may be of importance in aging and Alzheimer's disease (AD). Circadian disorders, such as sleep-wake cycle disturbances, are associated with aging, and even more pronounced in AD. Many studies have reported disrupted melatonin production and rhythms in aging and in AD that, as we showed, are taking place as early as in the very first preclinical AD stages (neuropathological Braak stage I-II). Degeneration of the retina-SCN-pineal axis may underlie these changes. Our recent studies indicate that a dysfunction of the sympathetic regulation of pineal melatonin synthesis by the SCN is responsible for melatonin changes during the early AD stages. Reactivation of the circadian system (retina-SCN-pineal pathway) by means of light therapy and melatonin supplementation, to restore the circadian rhythm and to relieve the clinical circadian disturbances, has shown promising positive results.

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The human pineal gland and melatonin in aging and Alzheimer's disease

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