الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Cognitive impairment (CI) results from modifiable and non-modifiable factors. Age and demographic and genetic factors are the major non-modifiable risk factors for the development of CI (Han et al., 2020). To date genetically, only some genes have been implicated in CI development including the Apolipoprotein (APOE)-ε4 allele, the sortilin-related receptor (SORL1) gene, brain derived neurotrophic factor (BDNF) and non-coding RNAs. APOE is a lipid-binding protein that is produced in humans as three common isoforms encoded by three alleles, APOE 2, 3, and 4. A substantial increase in the frequency of the APOE4 allele in AD patients and worse cognitive performance was reported compared to healthy controls (Eshkoor et al., 2015). Additionally, an APOE-4 allele is associated with a greater Aβ load in the brains of AD patients. This implies APOE interacts with Aβ, promoting plaque development (Liu et al., 2013).Sortilin-related receptor (SORL1) contributes in trafficking of amyloid precursor protein (APP) from the cell surface to the Golgi-endoplasmic reticulum complex. SORL1’s sub-cellular domain interacts with APP and guides it into recycling pathways. When SORL1 is under-expressed, APP is sorted into Aβ-generating compartments, increasing the risk of AD (Rogaeva et al., 2007).