The research community continues to make progress, slow but steady, in understanding the low-level biochemistry of neurodegenerative conditions. It is a very complex area of study. You might compare the research here, focused on amyloid, with results noted yesterday, focused on α-synuclein. The aging of the brain is accompanied by the aggregation of a number of altered proteins, producing solid deposits and a halo of surrounding changes in cell biochemistry that damage or kill brain cells. Beyond that summary, each is very different in mechanisms and outcome. Regardless, the end result is cognitive decline, a disruption of function in the brain. Control of protein aggregation is a major focus of the research community, but achieving any meaningful progress towards that goal has proven to been far more challenging than was hoped when these projects began in earnest.
The accumulation of amyloid peptides in the form of plaques in the brain is one of the primary indicators of Alzheimer's disease. While the harmful effects of amyloid peptide aggregates are well established, the mechanism through which they act on brain cells remains ill-defined. Researchers knew, for instance, that amyloid peptides disrupt synapses - the area of contact and chemical communication between neurons - but did not understand how they did so. Now, new findings have revealed the molecular mechanism that links amyloid aggregates and deficient synaptic function observed in animal models of Alzheimer's disease: peptide oligomers interact with a key enzyme in synaptic balance, thereby preventing its normal mobilization.
The molecule, called CamKII, usually orchestrates synaptic plasticity, an aspect of neuronal adaptability that enables neurons to reinforce their responses to the signals they exchange. Groups of neurons that code for an information to be memorized are connected by synapses, which are themselves under the control of mechanisms of synaptic plasticity. When the connection between two neurons must be reinforced in order to memorize information, for instance during intense stimulation, CamKII is activated and leads to a chain of reactions that strengthen the capacity to transmit messages between these neurons.
Synaptic plasticity is central to memory and learning. Amyloid peptides prevent CamKII from participating in this process of synaptic plasticity, and this blockage eventually leads to the disappearance of the synapse. This discovery could find an application in early phases of Alzheimer's disease when initial cognitive deficiencies are observed, which could be linked to this synaptic malfunction. The goal for researchers now is to continue studying amyloid aggregates, especially by trying to prevent their interaction with CamKII and the loss of synapses observed during the disease.