Choline Transporters and The Pathogenesis of Alzheimer's Disease

The deposition of senile plaques and neurofibrillary tangles in the brain are the prominent pathophysiology symptom of Alzheimer's disease (AD), in addition to diffuse brain atrophy. Several lines of evidence suggested a strong relationship between the degeneration of forebrain cholinergic neurons and pathogenesis of AD. AD is characterized by the disturbance of forebrain cholinergic system and by the dramatic decrease of acetylcholine (ACh), choline acetyltransferase, and a severe loss of cholinergic neurons. ACh is the only neurotransmitter released in the cholinergic synapses. Choline uptake via choline transporters is essential for ACh re-synthesis. Three types of transporters have been implicated in choline transporter family: high-affinity, Na+-dependent choline transporters (CHTs); intermediate-affinity, Na+-independent choline transporter-like proteins (CTLs) and polyspecific organic cation transporters (OCTs) with low affinity for choline. It has been shown that abnormal choline transporters are involved in a number of neurodegenerative disorders, including AD. The article aims to summarize the physiological role of choline transporter in the cholinergic system and pathological alterations in AD, providing new insight into the therapeutic treatment of AD.