The research centred on eukaryotic initiation factor 2 alpha (eIF2alpha) and two enzymes that modify it with a phosphate group; this type of modification is termed phosphorylation.
Study's senior author, Eric Klann, a professor in New York University's Center for Neural Science, and his colleagues hypothesized that abnormally high levels of eIF2alpha phosphorylation could become detrimental because, ultimately, protein synthesis would diminish, thereby undermining the ability to form long-term memories.
The researchers examined the neurological impact of two enzymes that phosphorylate eIF2alpha, kinases termed PERK and GCN2, in different populations of AD model mice - all of which expressed genetic mutations akin to those carried by humans with AD. These were: AD model mice; AD model mice that lacked PERK; and AD model mice that lacked GCN2.
They looked at eIF2alpha phosphorylation and the regulation of protein synthesis in the mice's hippocampus region and then compared these levels with those of post-mortem human AD patients.
The team found that both increased levels of phosphorylated eIF2alpha in the hippocampus of both AD patients and the AD model mice.
Moreover, in conjunction with these results, they found decreased protein synthesis, known to be required for long-term potentiation -- a form of long-lasting synaptic plasticity--and for long-term memory.
The study is published in the journal Nature Neuroscience.
--ANI (Posted on 12-08-2013)