P.5.a.006 Impact of Apo-E genotype on the response to donepezil therapy in patients with Alzheimer's disease

A recent paper reported that Aβoligomer causes neuronal cell death through the phosphatidylinositol-3-OH kinase (PI3K)-Akt-mTOR signaling pathway. Intraneuronal Aβ, a main pathological finding of Alzheimer's disease (AD), is also known as inhibiting activation of Akt. This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the Akt1 gene are associated with AD. SNPs genotyped using TaqMan technology was analyzed using a case-control study design. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls. Although two SNPs showed superficial positive, Hardy-Weinberg equilibrium (HWE) tests, and linkage disequilibrium (LD) analyses suggested that genetic regions of the gene are highly polymorphic. We failed to detect any synergetic association among Akt1 polymorphisms, Apolipoprotein E (APO E), and AD. Further genetic studies are needed to clarify the relationship between the Akt1 and AD.

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Apo E and apo E receptor gene expression in the brain of Alzheimer's disease subjects with different apoE genotype

Neurobiology of Aging ◽

10.1016/s0197-4580(00)82315-5 ◽

2000 ◽

Vol 21 ◽

pp. 115

Author(s):

Doris Dea ◽

Nicole Aumont ◽

Judes Poirier

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Receptor Gene ◽

Apoe Genotype ◽

Apo E ◽

The Brain ◽

Receptor Gene Expression

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β-hydroxybutyrate Impedes the Progression of Alzheimer’s Disease and Atherosclerosis in ApoE-Deficient Mice

Nutrients ◽

10.3390/nu12020471 ◽

2020 ◽

Vol 12 (2) ◽

pp. 471 ◽

Cited By ~ 3

Author(s):

Manigandan Krishnan ◽

Jong Su Hwang ◽

Mikyung Kim ◽

Yun Jin Kim ◽

Ji Hae Seo ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Therapeutic Potential ◽

Density Lipoprotein ◽

In Vitro Study ◽

Substantia Nigra Pars Compacta ◽

Apo E ◽

The Brain ◽

Deficient Mice

β-hydroxybutyrate (β-OHB) has been shown to exert an anti-inflammatory activity. Apolipoprotein-E (ApoE) is strongly associated with atherosclerosis and Alzheimer’s disease (AD). This study aimed to explore the therapeutic effect of β-OHB in the brain and the aorta of high-fat diet (HFD)-fed ApoE-deficient mice. We found in Apo-E deficient mice that β-OHB attenuated lipid deposition in the choroid plexus (ChP) and decreased amyloid plaque in the substantia nigra pars compacta. We also found decreased CD68-positive macroglia infiltration of the ChP in β-OHB-treated ApoE-deficient mice. β-OHB treatment ameliorated IgG extravasation into the hippocampal region of the brain. In vitro study using ChP mice cell line revealed that β-OHB attenuated oxidized low-density lipoprotein-induced ApoE-specific differentially expressed inflammatory ChP genes. Treatment with β-OHB reduced aortic plaque formation without affecting blood lipid profiles and decreased serum production of resistin, a well-established risk factor for both AD and atherosclerosis. Thus, the current study suggests and describes the therapeutic potential of β-OHB for the treatment of AD and atherosclerosis.

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