ABCA1  rs2230805 and rs2230806 common gene variants are associated with Alzheimer’s disease

Fehér, Ágnes; Giricz, Zsófia; Juhász, Anna; Pákáski, Magdolna; Janka, Zoltán; Kálmán, János

doi:10.1016/j.neulet.2017.11.027

Cited by 21 publications

(9 citation statements)

References 31 publications

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“…Candidate gene studies analyzing the R219K polymorphism (rs2230806) and AD risk have reported conflicting results. This variant was associated with an increased risk of AD in Caucasian [186][187][188][189] and Chinese [51] populations, found to be a protective variant to AD in Chinese-Han and Hungarian individuals [190,191], and found not to be associated with AD risk in the German population [192]. However, two meta-analyses failed to find significant associations between ABCA1 polymorphisms and AD [193,194].…”

Section: Abca1 In Neurological Diseasementioning

confidence: 99%

The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease

Jacobo-Albavera

Domínguez‐Pérez

Medina-Leyte

et al. 2021

IJMS

103

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Cholesterol homeostasis is essential in normal physiology of all cells. One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues. One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT). In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling. Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases. This review describes evidence obtained from animal models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections and in cancer progression.

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Section: Abca1 In Neurological Diseasementioning

confidence: 99%

The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease

Jacobo-Albavera

Domínguez‐Pérez

Medina-Leyte

et al. 2021

IJMS

103

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“…Methylation of specific CpG islands in the ABCA2 gene negatively associates with AD risk. ABCA2 mRNA expression might also be used to differentially diagnose mild cognitive impairment (MCI) from other forms of dementia (i.e., Huntington's disease) but not AD from MCI [93].…”

Section: The Pharmacogenomic Machinerymentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6–10 drugs/day with the consequent risk for drug–drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 geno-phenotypes are involved in the metabolism of over 90% of drugs currently used in patients with dementia, and only 20% of the population is an extensive metabolizer for this tetragenic cluster. ADRs associated with anti-dementia drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, and antiepileptic drugs can be minimized by means of pharmacogenetic screening prior to treatment. These drugs are substrates, inhibitors, or inducers of 58, 37, and 42 enzyme/protein gene products, respectively, and are transported by 40 different protein transporters. APOE is the reference gene in most pharmacogenetic studies. APOE-3 carriers are the best responders and APOE-4 carriers are the worst responders; likewise, CYP2D6-normal metabolizers are the best responders and CYP2D6-poor metabolizers are the worst responders. The incorporation of pharmacogenomic strategies for a personalized treatment in dementia is an effective option to optimize limited therapeutic resources and to reduce unwanted side-effects.

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“…The adenosine triphosphate-binding cassette transporter A1 ( ABCA1 ) and A7 ( ABCA7) encode lipid floppases that transfer lipids from the inner leaflet to the outer leaflet of the cell membrane making them available for export to APOE acceptor particles (Tarling et al, 2013; Turton and Morgan, 2013; Wahrle et al, 2004). Further, nonsense variants in both ABCA1 and ABCA7 have been associated with increased risk of developing AD (Bossche et al, 2016; Chang et al, 2019; Chen et al, 2016; Fehér et al, 2018; Teresa et al, 2020). ABCA7 has also been identified as an AD risk locus in GWAS and is known to facilitate clearance of amyloid-β (Aikawa et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Neuronal ROS-Induced Glial Lipid Droplet Formation is Altered by Loss of Alzheimer’s Disease-associated Genes

Moulton

Barish

Ralhan

et al. 2021

Preprint

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A growing list of Alzheimers disease (AD) genetic risk factors is being identified, but the contribution of these genetic mutations to disease remains largely unknown. Accumulating data support a role of lipid dysregulation and excessive ROS in the etiology of AD. Here, we identified cell-specific roles for eight AD risk-associated genes in ROS-induced glial lipid droplet (LD) formation. We demonstrate that ROS-induced glial LD formation requires two ABCA transporters (ABCA1 and ABCA7) in neurons, the APOE receptor (LRP1), endocytic genes (PICALM, CD2AP, and AP2A2) in glia, and retromer genes (VPS26 and VPS35) in both neurons and glia. Moreover, ROS strongly enhances Aβ42-toxicity in flies and Aβ42-plaque formation in mice. Finally, an ABCA1-activating peptide restores glial LD formation in the APOE4-associated loss of LD. This study places AD risk factors in a neuron-to-glia lipid transfer pathway with a critical role in protecting neurons from ROS-induced toxicity.

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ABCA1 rs2230805 and rs2230806 common gene variants are associated with Alzheimer’s disease

Cited by 21 publications

References 31 publications

The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease

The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Neuronal ROS-Induced Glial Lipid Droplet Formation is Altered by Loss of Alzheimer’s Disease-associated Genes

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