Pineal gland dysfunction in Alzheimer's disease: relationship with the immune-pineal axis, sleep disturbance, and neurogenesis

Abstract

Alzheimer's disease (AD) is a globally common neurodegenerative disease, which is accompanied by alterations to various lifestyle patterns, such as sleep disturbance. The pineal gland is the primary endocrine organ that secretes hormones, such as melatonin, and controls the circadian rhythms. The decrease in pineal gland volume and pineal calcification leads to the reduction of melatonin production. Melatonin has been reported to have multiple roles in the central nervous system (CNS), including improving neurogenesis and synaptic plasticity, suppressing neuroinflammation, enhancing memory function, and protecting against oxidative stress. Recently, reduced pineal gland volume and pineal calcification, accompanied by cognitive decline and sleep disturbances have been observed in AD patients. Here, I review current significant evidence of the contribution of pineal dysfunction in AD to the progress of AD neuropathology. I suggest new insights to understanding the relationship between AD pathogenesis and pineal gland function.

Keywords: Alzheimer’s disease (AD); Circadian rhythms; Immune-pineal axis; Melatonin; Pineal calcification; Pineal gland.

Fig. 1

The schematic diagram of pineal gland dysfunction in AD, immune-pineal axis, and the role of melatonin in neurogenesis. a Pineal calcification and reduced pineal volume causes pineal dysfunction, which are commonly observed in AD brain. The pineal dysfunction leads to the reduction of melatonin level, subsequently results in sleep deficit. b Immune cells could regulate NF-κB activation and promote the production of melatonin in pinealocytes through CREB-AANAT signaling. c The decreased melatonin level leads to the impairment of neurogenesis in AD, because reduced melatonin level contributes the reduction of BDNF and GDNF expression, which are known as boosters in neurogenesis