Table 2. Summarizing association between mutations in cholesterol metabolism protein and Alzheimer's disease .

LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TC: total cholesterol; TG: triglycerides; AD: Alzheimer's disease; Apo: apolipoprotein; Aβ: beta-amyloid; APP: amyloid precursor protein; MCI: mild cognitive impairment; BBB: blood-brain barrier; 24S HC: 24S hydroxycholesterol; 27O-HC: 27O hydroxycholesterol; PSEN: presenilin; ABCA1 and ABCA7: ATP binding cassette transporter 1 and 7; CYP46A1: cytochrome P450 family 46 subfamilies A member 1

Author	Year of Publication	Type of Study	Purpose of Study	Intervention Studied	Result/Conclusion
Wings et al. [8]	2019	Case-control study	To determine if plasma cholesterol and genetic variants of various cholesterol transport proteins are associated with AD.	Total cholesterol, LDL-C, HDL-C, TG, and genetic variants in ApoB, ApoE, APP, PSEN1 and PSEN2.	Primary outcome: the relationship between plasma cholesterol and AD was seen. Secondary outcome: AD was associated with mutations in APOE, APP, PSEN1, PSEN2, and APOB.
Jeong et al. [6]	2019	Literature review	To determine if APOE induced cholesterol dysfunction affects the various brain cells and causes AD.	APOE4, APOE3, APOE2 alleles	APOE ɛ4 one or more alleles increase the risk of AD
Li et al. [48]	2017	Case-control study	To determine if the ABCA7 genotype of cholesterol transport protein it's associated with sporadic AD	ABCA7 genotyping	ABCA7 genotype was associated with lipid homeostasis and AD.
Yassine et al. [16]	2016	Cross-sectional study	To determine if ABCA-1 mediated cholesterol efflux is affected in patients with AD and MCI	CSF's role in cholesterol transport was assessed using a BHK cell line that expressed the ABCA1 transporter.	In case of MCI and AD, the role of CSF was impaired. ABCA1‐mediated cholesterol efflux does not take place as normal, leading to AD.
Agarwal et al. [45]	2014	Meta-analysis	To determine the association between ApoE alleles and the risk for AD	APOE genotyping	All genotypes of the ApoE e4 allele, increase the risk of AD, although the ApoE e2, e3 alleles protect from AD.
Toro et al. [44]	2014	Cohort study	To determine the association of total cholesterol in AD and MCI and the ApoE genotype	Total cholesterol	High TC levels are associated with AD but are independent of the APOE genotype.
Lukiw [49]	2014	Literature review	To determine if cholesterol and 24 hydroxycholesterol trafficking in the brain causes AD and CYP46A1 gene effects on AD	Cholesterol and 24 hydroxycholesterol, beta-amyloid plaques, CYP46A1 genotyping	Beta-amyloid plaques, which is characteristic of AD, were found with increased CSF 24 hydroxycholesterol, a mutation in the CYP46A1 gene causes dysfunctional cholesterol metabolism
Caramelli et al. [47]	1999	Case-control study	To determine the relationship between plasma lipids and AD.	VLDL, HDL-C, LDL-C, triglycerides, ApoB, lipoprotein (a)	Significantly higher Apolipoprotein B levels were found in AD patients, whereas the concentration of lipoprotein (a) and plasma lipids was not statistically different. This shows that APOE may not be the only transporter associated with AD.
Raygani et al. [46]	2006	Case-control study	To determine the association between plasma lipids, ApoE polymorphism, and with AD	HDL-C, LDL-C, TC, APOB, APOE4, APOA1	Apolipoprotein e4 is associated with AD. Also, decreased ApoA1, HDL-C, increased ApoB, increased LDL-C, TC is seen in AD
Panza et al. [10]	2006	Literature review	To determine the association between TC, 24 S hydroxycholesterol, LDL-C, Lp(A), ApoE levels with AD	TC, 24S HC, LDL-C, Lp(A), APOE	TC, LDL-C, Lp(A) was found to be elevated in patients with AD. No consistent association between ApoE and AD have been found in this study
Martins et al. [5]	2006	Literature review	To understand cholesterol mechanism, the relation between APOE allele and AD, determine convergence risk factors for AD and CAD	APOE ɛ4 allele	APOE ɛ4 one or more alleles increase the risk of AD. A decrease in APO A1 is associated with AD.
Kivipelto et al. [43]	2002	Cohort study	To determine the association between APOE ɛ4 allele and AD	APOE genotype	APOE ɛ4 alleles are associated with AD