The apoE gene is located on chromosome, and the protein consists of three isoforms occurring in varying frequency among the general population: apoE. ApoE is normally circulating in plasma and is a constituent of plasma lipoprotein particles mediating uptake of those into the cells. In AD, microglial cells surrounding the core of senile plaques, extracellular deposits of aggregated amyloid, are positive for apoE protein. The variations are probably due to differences in methodology and patient materials.Differences in the apoE isoforms have also been shown.The apoE isoform is associated as a cysteine susceptibility gene for AD, which might be related to confounding factors interfering with sample handling andor analyses.This change was detected in CSF of AD patients, reecting the increased frequency of the apoE allele in this population.A correlation was found between synaptic loss and severity of dementia, which suggest a close relationship between synaptic pathology and the cognitive decline in AD. The synaptic vesicle proteins raba, synaptotagmin, and synaptophysin, the presynaptic protein GAP and the postsynaptic protein neurogranin have all been found to be reduced in the frontal, temporal, and parietal cortex and hippocampus in AD compared to controls. Reduced levels of synaptic vesicle proteins have also been found in several other studies. Synaptic proteins in CSF might be useful as markers of the synaptic degeneration.However, most synaptic proteins are membrane proteins with low water solubility and are present in very low concentration in CSF.Attempts to dene synaptic pathology in CSF came rst from other markers of synapses such as chromogranin A and ganglioside GM, which were shown to be reduced in AD patients compared to controls. Benzocaine Previously, one synaptic vesicle protein, synaptotagmin, was for the rst time detected in CSF using a procedure including afnity chromatography followed by microreversed phase chromatography, and enhanced chemiluminescences immunoblotting. A reduction of synaptotagmin was rst found in both brain tissue and also in lumbar CSF of in AD patients, implying that CSF reects the composition of synaptic proteins in the brain under normal and pathological conditions.Other synaptic proteins were not detectable using this procedure.LPIEF in combination with immunoblotting has been used for enrichment and detection of neuronspeci c proteins that are involved in neurodegenerative disorders. Six synaptic proteins including raba, synaptotagmin, GAP, SNAP, synapsin, and neurogranin were detected in nanogram per litre quantities in human CSF using this method.These results showed that several of the synaptic proteins could be identied in CSF in trace amounts, showing that these proteins can be quantitative, which may reect altered synaptic function and integrity as it is known to occur in neurodegenerative diseases.Therefore, a sandwichELISA was developed for determination of one synaptic vesicle protein, phosphosynapsin, in individual CSF samples. The sandwichELISA was based on a rabbit antiphosphosynapsin antibody and a synapsin specic mono P.Using this assay, phosphosynapsin was determined in CSF of AD patients and controls.The level of phosphosynapsin was increased in AD group. Phospho synapsin levels in almost all controls were so low that the proteins could not be detected with our ELISA method.Earlier attempts to measure synapsin in individual CSF samples also showed undetectable levels in healthy individuals.