ABSTRACT
Research on the many contributing factors to the development of Alzheimer’s disease (AD) has branched into many paths, in the attempt to hunt down the biochemical bases for pathological biochemical changes in brain tissue that lead to synaptic and neuronal destruction. One path has led to study of aberrant biometal metabolism associated with AD. Metals are intriguing because the pathologic amyloid plaques that build up in AD brains are rich in copper, zinc, and iron (Adlard and Bush 2006). Zinc also plays a major role in inhibitory modulation of the N-methyl-D-aspartate (NMDA) receptor site, as will be detailed in ZnT3: The Major Zinc Transporter. Without adequate zinc (Zn2+), there is incompetent inhibition of NMDA receptors leading to excessive excitatory glutamate activity. This allows too much calcium into cells, leading to neurotoxicity and cell death. NMDA receptor overactivity is thought to play a leading role in the neurodegeneration seen in AD (as well as other neurodegenerative diseases; review in Gardoni and Di Luca 2006).
