Table 1. Summarizing the association between plasma lipids and AD.

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; MCI: mild cognitive impairment; BBB: blood-brain barrier; 24S HC: 24S hydroxycholesterol; 27O-HC: 27O hydroxycholesterol; PC: phosphatidylcholine; PLA2: phospholipase 2

	Author	Year of Publication	Type of Study	Purpose of Study	Intervention Studied	Result/Conclusion
1.	Saiz-Vazquez et al. [35]	2020	Meta-analysis	To determine the association of serum cholesterol and AD.	Total serum cholesterol, HDL-C, LDL-C, and serum triglycerides	The relation between increased LDL-C and AD was found. No association between TC, TG, HDL-C, and AD were found.
2.	Zhou et al. [37]	2020	A systematic review and meta-analysis	To determine the association of serum cholesterol and AD.	LDL-C was measured	Elevated LDL-C leads to AD. This association is more in patients 60–70 years of age and gradually declines with age.
3.	Iqbal et al. [24]	2020	Systematic review	To determine the association of serum lipids and AD	HDL-C, LDL-C, TG, TC	HDL-c was found to be low, whereas LDL-C, TG, TC were high in cases of AD.
4.	Bernath et al. [40]	2020	Cross-sectional study	To determine the association of triglycerides with AD	Serum TG	Serum TG was found to be high in cases of AD
5.	Jensen et al. [28]	2020	Randomized control trial	To determine if physical exercise influences the lipid profile and AD	HDL-C, TC, LDL-C, triglycerides	With an increase in physical activity, cholesterol was lower, thus decreasing the risk of AD.
6.	Chew et al. [22]	2020	Literature review	To determine the factors affecting lipid metabolism and the association between plasma lipids and AD.	Age, sex, race, diet, plasma lipids level	Decreased plasma HDL-C and increased triglyceride is associated with AD.
7.	Liu et al. [39]	2019	Meta-analysis	To determine the association between plasma cholesterol and AD	Total serum cholesterol, HDL-C, LDL-C, and serum triglycerides	Serum LDL-C and total cholesterol were found to be elevated in AD. No association between HDL-C and triglycerides was found.
8.	Wu et al. [38]	2019	Meta-analysis	To determine the association between plasma lipids and AD	HDL-C, TC, LDL-C	LDL-C, TC are increased in AD
9.	Costa et al. [42]	2019	Case-control study	To determine the association between phospholipids and AD, and the activity of PLA2 in the brain	Serum phospholipids, PLA2 by radio enzymatic assay	Ten serum phospholipids were assessed and found to decrease in AD; PLA2 activity was also decreased in the neuronal membrane in AD.
10.	Anstey et al. [34]	2017	A systematic review and meta-analysis	To determine the association between plasma lipids and AD in midlife	HDL-C, LDL-C, TC, TG	Increased TC in midlife is found to be associated with late-onset AD. No association between HDL and TG with AD was found.
11.	Proitsi et al. [25]	2017	Case-control study	To determine the association between plasma cholesterol and AD and the associated brain atrophy	Plasma lipids. Brain – left/right hippocampal area, entorhinal cortex	Increased plasma lipids were associated with AD, causing brain atrophy.
12.	Wong et al. [20]	2017	Literature review	To determine the progress in lipidomics research in AD with the help of mass spectrometry	Phospholipids, sphingolipids, and cholesterol	Increase total cholesterol increase the risk of AD. Sphingolipids: in CSF – sphingomyelin levels increase in prodromal AD, ceramide increases in AD, sulfatide decreases in AD. As blood – ceramide level increases, sphingomyelin decreases in AD. Phospholipids: increases in CSF and decreases in blood in AD.
13.	Wang et al. [11]	2016	Meta-analysis	To determine if 24S-HC and 27 O HC are biomarkers for AD	24S-HC, 27S-HC	24S-HC and 27O-HC are sensitive biomarkers for AD diagnosis
14.	He et al. [32]	2016	Case-control study	To determine the association of plasma lipids with MCI in the elderly	Total cholesterol, HDL-C, LDL-C, serum triglycerides were measured	TC was elevated in the elderly with AD. No association between LDL-C and AD was found. HDL-C and TG were negatively related to AD.
15.	Hall et al. [31]	2014	Systematic review	To determine if increased cholesterol in AD is gender-specific	Total serum cholesterol	Males were found to have higher total Cholesterol in AD
16.	Toro et al. [44]	2014	Cohort study	To determine the association of total cholesterol in AD and MCI and the ApoE genotype	Total cholesterol	Increased TC is seen in patients with MCI and AD even before symptom scan arise. This is independent of the APOE genotype.
17.	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
18.	Reitz and Mayeux [4]	2014	Literature review	To determine the genetic and non-genetic risk factor of AD	Plasma and CSF lipid markers, genetic mutations, age, physical activity, BMI, cerebrovascular disease.	Cholesterol was found to be increased in cases of AD.
19.	Popp et al. [41]	2013	Case-control study	To determine the association between cerebral and extracerebral cholesterol and its relation with AD.	Plasma and CSF cholesterol, cholesterol precursors, 24 hydroxycholesterols, and 27 hydroxycholesterols were measured.	Cholesterol synthesis was found to be de novo in the brain. Twenty-four hydroxycholesterols were found to increase in the case of AD.
20.	Kosicek and Hecimovic [17]	2013	Literature review	To determine the association between phospholipids and AD	Sulfatide, ceramide, sphingomyelin, PC	Sphingomyelin increases in the prodromal stage of AD, ceramide increases, Sulfatide decreases, and PC metabolites decreased in AD.
21.	Formiga et al. [27]	2012	Cohort study	To determine the association of HDL-C levels with mental, physical activity, and cognition	HDL-C	Decreased HDL-C was only found to improve functional aspect but not cognitive performance
22.	Helzner  et al. [29]	2009	Cohort study	To determine the role of vascular risk factors in AD.	Total cholesterol, HDL-C, LDL-C	High total cholesterol and LDL-C levels and diabetes cause an increased incidence of AD, thus confirming that vascular risk factors play a role in AD.
23.	Mamo et al. [13]	2008	Case-control study	To investigate if lipoproteins are bound to Aβ isoforms	Fasting state lipoproteins	The majority of plasma triglycerides, VLDL, and IDL, was bound to Aβ1–40 isoform
24.	Solomon et al. [33]	2007	Case-control study	To determine the association between TC and AD	TC	Serum TC increases in midlife in AD and later decreases with age.
25.	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 Apo B, increased LDL-C, TC is seen in AD.
26.	Solfrizzi et al. [30]	2006	Literature review	To determine the association between biomarkers such as HDL-C, TC, LDL-C, homocysteine, lipoprotein A, inflammatory cytokines, and AD	HDL-C, LDL-C, TC, triglycerides, homocysteine, LP(A), cytokines	All these biomarkers were found to increase in association with AD
27.	Sabbagh et al. [15]	2005	Case-control study	To determine the association between plasma lipids and AD	HCL-C, LDL-C, TC, TG, TOTAL/HDL RATIO	Increased TC, TG, LDL-C was associated with AD. HDL-C and total/HDL ratio remains normal in AD.
28.	Wolf et al. [26]	2004	Randomized control trial	To determine the association between hippocampal volume (presumptive index of AD) and plasma lipids	Plasma HDL-C, LDL-C, TC were studied	HDL-C was found to be associated with hippocampal volume in the brain.
29.	Pappolla et al. [23]	2003	Cohort study	To determine the association between amyloid plaques and hypercholesterolemia	Amyloid deposits using imaging and immunohistochemistry and serum cholesterol	Association was seen between hypercholesterolemia and beta-amyloid plaques deposited in the human brain
30.	Kuo et al. [7]	1998	Case-control study	To determine if elevated LDL-C in AD is related to beta-amyloid 1-42	TC, HDL-C, LDL-C, lipoproteins, ApoB	A correlation was found between the levels of serum total cholesterol, LDL-C, and ApoB with only Aβ N-42 in AD, not Aβ N-40.
31.	Moroney et al. [36]	1999	Cohort study	To determine the effect of lipids on dementia with stroke	HDL-C, LDL-C, triglycerides, total cholesterol, lipoprotein A, APOE4.	Increased plasma LDL-C was found in patients with dementia with stroke, but its relationship with the ApoE4 allele was not established.