Are Patients with Darier and Haily-Haily Diseases Susceptible to Alzheimer's Disease? A Theory Based on Abnormal Intraneuronal Ca 2+ Homeostasis

Abstract

Calcium is one of the most important intracellular messengers in human brain. Studies show that there is a relationship between altered Ca²⁺-homeostasis, especially elevation of intracellular calcium, and formation of the hallmark pathological lesions of Alzheimer's disease. Additionally, Ca²⁺ is crucial for normal function of the skin, and an abnormal rise in intracellular Ca²⁺ can consequently lead to the development of two skin disorders: Darier and Hailey-Hailey diseases. As these mutated genes are also highly expressed in the brain and these patients are reported to experience some neuropsychiatric problems, we have hypothesized that patients with these dermatologic diseases may be more prone to the development of Alzheimer's disease. Further investigation may give us clues to find novel therapeutic targets and agents for modulation of intracellular calcium in neurons.