Effect of Marcks Concentration on Cognition

Research has determined that ageing is important to consider when looking at neurodegenerative diseases and there cause, such as Alzheimer’s disease. It is thought that neuronal loss is primarily involved in neurodegeneration when in fact it seems that synaptic strength, or plasticity, is more vulnerable to the process of ageing (1). Biochemical and structural alterations of the synapse such as changes in lipid composition in certain areas of the brain are also thought to be associated with this deterioration (2, 3, 4). In this paper, the lipid of concern is the versatile phosphatidylinositol 4,5-bisphosphate (PIP2), which is important for signalling proteins, generation of secondary messengers that go on to regulate other physiological processes, as well as being responsible for the activation of some ion channels and enzymes and assisting in trafficking of proteins to the cell membrane (5, 8). Why is PIP2 then so important in hippocampal cells? PIP2 is a substrate for hydrolysis by the enzyme phospholipase C (PLC), whereby the products of this interaction are the secondary messengers, diacyl Glycerol (DAG) and inositol trisphosphate (IP3) (6, 8) that are involved in the regulation of physiological processes on the plasma membrane including calcium mobilisation, which all contribute to mediation of synaptic plasticity (7).

This would suggest that low PIP2 levels in the hippocampus would result in synaptic plasticity deficits as a result. Research has been conducted into PIP2’s involvement in reduced cognition in older brains using the synaptosomes isolated from mice at 4 months, 10 months and 20 months old. The results obtained showed that older mice had low levels of PIP2 in the hippocampus as well as high levels of the phosphorylation product of PIP2 called PIP3 and low levels of PLC. The authors suggest that the low levels of PIP2 could be due to it being consumed to produce phosphatidylinositol (3,4,5)-trisphosphate (PIP3). The predominance of PIP3 in older