The current meta-analysis of the cohort review was designed to elucidate the progress made in neuroproteomics of the synaptosome. The association of the comprehensive synaptic proteome and its link to physiological or pathological setting is rapidly mounting. Chemical synapses in the brain are focal hot spots for interneuronal signalling, signal transduction, and its plasticity. Structurally, synapses comprise axon termini or the presynapse (vesicles filled with neurotransmitters that function as molecular signals), synaptic clefts (extracellular matrix and adhesion molecules), and Postsynaptic Density or PSD (with receptors for neurotransmitters that rely upon the chemical signalling). The pre- and post-synaptic clefts are responsible for mediating and regulating neurotransmitter release, their receptor binding, and perception rely on chemical signals. Moreover, short- and long-term structural and functional alterations that are necessary for the optimal higherorder brain functions are also mainly dependent on the protein dynamics at the synapses. Not surprisingly, disruptions in synaptic physiology are considered as the major pathogenic mechanisms underlying the progression of several neurodegenerative disorders, including Alzheimer's disease. This review briefly discusses the subcellular fractionation protocols and the related biochemical approaches for the isolation of synaptic compartments. Besides, it discusses the progress made in understanding the pathological alterations in the synaptic proteome in neurodegenerative disorders, particularly focussing on Alzheimer's disease dementia.