Research Projects

i. There is growing evidence that age-related changes in aging brain are linked to microstructural alterations in brain connections apart from the neuronal loss, including decline in the number of myelinated nerve fibres, change in their diameters, deterioration of myelin coating, and change in the shape of the dendritic arbour, spines, and synapses (Collin & van den Heuvel, 2013). ii. Different brain regions myelinate at varying time periods during the normal development of central nervous system (CNS). The spinal cord and brain stem typically myelinate first, followed by other regions like the telencephalon, entorhinal cortex, hippocampus, and amygdala. Additionally, areas that are myelinated at later ages have a higher risk of demyelination, a condition known as "neuropathologic retrogenesis” and has been seen in AD. iii. When compared to patients without dementia, postmortem brain tissue from AD patients exhibited chemical changes in the white matter, indicating myelin loss. The concentrations of fatty acids in white matter are also changed in AD. iv. Cholesterol is one of the essential components of lipid rafts, which are necessary for the formation of synaptic vesicles as well as for the clustering and localization of receptors for neurotransmission at pre- and post-synaptic membranes, respectively, thereby playing a significant role in the regulation of synaptic function in the brain (Allen et al., 2007; Thiele et al., 2000). With 25% of the body's total cholesterol pool, the human brain is the most cholesterol-rich organ (Giudetti et al., 2016). v. Cholesterol has also been found to play a role in the processing of amyloid precursor protein (APP), thereby, amyloid beta (Aβ) accumulation. (Dason et al., 2014; van Deijk et al., 2017) vi. Numerous single nucleotide polymorphisms in these genes that are involved in the various steps of cholesterol homeostasis appear to be associated with an increased risk of Alzheimer's disease, according to evidence from the literature. Some of the examples include rs3931914 and rs3761740 in the HMGCR gene, rs1800977 and rs2422493 in the ABCA1 gene, etc. (Rodríguez-Rodríguez et al., 2009) vii. However, most of these studies do not include the south-asian population, particularly Indian population. The number of similar studies in India is also negligible with most of the studies focusing only on ApoE gene polymorphisms in AD. • This study would be a proof of concept to determine the allelic distribution of selected gene polymorphisms involved in demyelination process and/or cholesterol homeostasis pathway in patients suffering from Alzheimer’s Disease (AD), specifically in North India.