An <i>Apolipoprotein A-I</i> Gene Promoter Polymorphism Associated with Cognitive Decline, but Not with Alzheimer’s Disease

Abstract

Background/Aims: Accumulating biological and epidemiological evidence suggests a close link between cholesterol metabolism and the pathophysiology of Alzheimer’s disease (AD). The observation that the use of statins reduces the risk of AD sustains this hypothesis. Apolipoprotein A-I (APOA1) is the major component of the high-density lipoproteins, particles involved in reverse cholesterol transport. Therefore, genetic polymorphisms in the gene encoding APOA1 might influence cholesterol metabolism and be a risk factor for AD. A previous study suggested an impact of a G→A polymorphism at position –75 bp in the APOA1 gene on the risk for early-onset AD and on the age at onset of the disease. We studied this polymorphism in 3 independent European population samples. Methods: Genotyping was conducted asdescribed in the previous study. Results: We were unable to show any impact of this polymorphism on the risk of AD. Conversely, subjects bearing the A allele of this polymorphism were at risk of cognitive decline. Conclusion: Our resultssuggest an impact of the G→A polymorphism at position –75 bp in the APOA1 gene on cognitive impairment, but not on the risk of AD.

Apolipoproteins and HDL cholesterol do not associate with the risk of future dementia and Alzheimer’s disease: the National Finnish population study (FINRISK)

“…All the analyses were performed using Bsurvival^, Bmeta^, Bmediate^, Betm^, Bcmprsk,^and Bmice^packages of R vers. 3.2.3 software (Buuren and Groothuis-Oudshoorn 2011;Allignol et al 2011;Team 2013;Therneau 2014;Tingley et al 2014;Gray 2014;Schwarzer 2015).…”

Overexpression of Human Apolipoprotein A-I Preserves Cognitive Function and Attenuates Neuroinflammation and Cerebral Amyloid Angiopathy in a Mouse Model of Alzheimer Disease

“…In contrast, two other studies report that increased levels of apoA-I/HDL may increase the risk of AD; one shows that increased HDL cholesterol levels are associated with an increasing number of amyloid plaques in human brain (50), whereas the other shows that a polymorphism in the promoter of the apoA-I gene that increases plasma apoA-I level is associated with an earlier onset of non-familial AD (20). However, a more recent study reports no association between this polymorphism and AD (21).…”

“…ApoA-I has also been shown to bind A␤ in the CSF and plasma (16 -18) and to bind fulllength APP (19). In addition, apoA-I polymorphisms have been associated with AD and/or dementia (20,21). Furthermore, epidemiological studies show a marked decrease of plasma apoA-I levels in human AD patients (22) and demonstrate that decreased HDL cholesterol and serum apoA-I concentrations are highly correlated with the severity of AD (23).…”

Cerebrospinal Fluid Particles in Alzheimer Disease and Parkinson Disease

“…In sharp contrast to apoE, apoAI is not synthesized in the CNS and its presence in CSF indicates transit across the blood-brain barrier (124). Polymorphisms in the gene that encodes apoAI have been correlated with AD dementia or all-cause dementia (19, 20); plasma and serum apoAI levels are decreased in patients with AD dementia (22–24); and serum levels of apoAI have been associated inversely with risk of AD dementia (21). Furthermore, recent studies have shown the lack of apoAI increases cerebral amyloid angiopathy and memory deficits of AD dementia (125), and increasing plasma apoAI levels provides cognitive and neuropathological benefits in animal models of AD dementia (126).…”

“…Aβ peptides do bind apoE-containing CSF lipoproteins, but not apoE itself (17, 18). Polymorphisms in the apoAI gene are associated with dementia (19, 20), and apoAI plasma or serum levels are inversely associated with AD dementia and PD (21–27). ApoAI also is reported to bind Aβ in CSF and plasma.…”