scholarly journals Effects of functional variants of vitamin C transporter genes on apolipoprotein E E4-associated risk of cognitive decline: The Nakajima study

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259663
Author(s):  
Koji Hayashi ◽  
Moeko Noguchi-Shinohara ◽  
Takehiro Sato ◽  
Kazuyoshi Hosomichi ◽  
Takayuki Kannon ◽  
...  
Keyword(s):  
Vitamin C ◽  
Cognitive Decline ◽  
Apolipoprotein E ◽  
Minor Allele ◽  
Cognitively Impaired ◽  
Single Nucleotide Variants ◽  
Altered Expression ◽  
Functional Variants ◽  
Major Allele ◽  
The Brain

Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case–control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05–3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05–5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58–6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain.

Higher Blood Vitamin C Levels are Associated with Reduction of Apolipoprotein E E4-related Risks of Cognitive Decline in Women: The Nakajima Study

2018 ◽  
Vol 63 (4) ◽  
pp. 1289-1297 ◽  
Author(s):  
Moeko Noguchi-Shinohara ◽  
Chiemi Abe ◽  
Sohshi Yuki-Nozaki ◽  
Chiaki Dohmoto ◽  
Ayaka Mori ◽  
...  
Keyword(s):  
Vitamin C ◽  
Cognitive Decline ◽  
Apolipoprotein E

Inflammatory Pathways Are Impaired in Alzheimer Disease and Differentially Associated With Apolipoprotein E Status

2021 ◽  
Author(s):  
Courtney M Kloske ◽  
Adam J Dugan ◽  
Erica M Weekman ◽  
Zachary Winder ◽  
Ela Patel ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Apolipoprotein E ◽  
Microglial Activation ◽  
Middle Temporal Gyrus ◽  
Altered Expression ◽  
Apoe Ε4 ◽  
Apoe Isoforms ◽  
Expression Of Genes ◽  
Underlying Mechanisms ◽  
The Brain

Abstract Alzheimer disease (AD) is a neurodegenerative disease characterized by a cognitive decline leading to dementia. The most impactful genetic risk factor is apolipoprotein E (APOE). APOE-ε4 significantly increases AD risk, APOE-ε3 is the most common gene variant, and APOE-ε2 protects against AD. However, the underlying mechanisms of APOE-ε4 on AD risk remains unclear, with APOE-ε4 impacting many pathways. We investigated how the APOE isoforms associated with the neuroinflammatory state of the brain with and without AD pathology. Frozen brain tissue from the superior and middle temporal gyrus was analyzed from APOE-ε3/3 (n = 9) or APOE-ε4/4 (n = 10) participants with AD pathology and APOE-ε3/3 (n = 9) participants without AD pathology. We determined transcript levels of 757 inflammatory related genes using the NanoString Human Neuroinflammation Panel. We found significant pathways impaired in APOE-ε4/4-AD individuals compared to APOE-ε3/3-AD. Of interest, expression of genes related to microglial activation (SALL1), motility (FSCN1), epigenetics (DNMT1), and others showed altered expression. Additionally, we performed immunohistochemistry of P2RY12 to confirm reduced microglial activation. Our results suggest APOE-ε3 responds to AD pathology while potentially having a harmful long-term inflammatory response, while APOE-ε4 shows a weakened response to pathology. Overall, APOE isoforms appear to modulate the brain immune response to AD-type pathology.

scholarly journals Reversing Mitochondrial, Metabolic and Molecular Defects in the Brain Improves Cognition in Aged Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 857-858
Author(s):  
Rajagopal Sekhar ◽  
Premranjan Kumar
Keyword(s):  
Oxidative Stress ◽  
Cognitive Decline ◽  
Whole Body ◽  
Cognitively Impaired ◽  
The Novel ◽  
Open Label ◽  
Molecular Defects ◽  
Aged Mice ◽  
Systemic Insulin Resistance ◽  
The Brain

Abstract Age-associated cognitive-decline is a risk factor for Alzheimer’s disease (AD), but mechanisms are not well understood, and interventions are lacking. Rodent studies on AD have not led to therapeutic breakthroughs for cognitively-impaired humans. In an open-label trial in older-adults we found that supplementing GlyNAC (glutathione precursors glycine and N-acetylcysteine) improved cognitive-decline, defects in whole-body mitochondrial-function, and systemic insulin-resistance, oxidative-stress, and inflammation. We hypothesized that aged-mice will have similar defects in the brain, and studied male C57BL/6J mice as follows: young-mice (20w) were compared to two-groups of aged-mice (90-weeks) receiving either GlyNAC or isonitrogenous-placebo diets for 8-weeks. GlyNAC-supplementation improved cognition, and the following measures in the brain: glutathione-concentrations, glucose-transporters in blood-brain-barrier and neurons, mitochondrial glucose-oxidation, oxidative-stress, endoplasmic-reticulum stress, autophagy, mitophagy, inflammation, senescence, genomic and telomere damage. These data provide mechanistic insights into the novel and beneficial role of GlyNAC supplementation to reverse cognitive-decline in aging, and holds promise for human AD.

scholarly journals P3-546: HIGHER BLOOD VITAMIN C LEVELS ARE ASSOCIATED WITH REDUCED RISK OF COGNITIVE DECLINE IN APOLIPOPROTEIN E E4-POSITIVE WOMEN: THE NAKAJIMA STUDY

2019 ◽  
Vol 15 ◽  
pp. P1182-P1183
Author(s):  
Moeko Shinohara ◽  
Chiemi Abe ◽  
Sohshi Yuki-Nozaki ◽  
Chiaki Dohmoto ◽  
Ayaka Mori ◽  
...  
Keyword(s):  
Vitamin C ◽  
Cognitive Decline ◽  
Apolipoprotein E ◽  
Reduced Risk

Atheromatosis Extent in Coronary Artery Disease is not Correlated with Apolipoprotein-E Polymorphism and its Plasma Levels, but Associated with Cognitive Decline

2010 ◽  
Vol 999 (999) ◽  
pp. 1-8 ◽  
Author(s):  
Luciana Moreira Lima ◽  
Maria das Gracas Carvalho ◽  
Claudia Natalia Ferreira ◽  
Ana Paula Fernandes ◽  
Cirilo Pereira da Fonseca Neto ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cognitive Decline ◽  
Apolipoprotein E ◽  
Plasma Levels ◽  
Apolipoprotein E Polymorphism ◽  
Artery Disease

scholarly journals Cognitive trajectories of patients with focal ß-amyloid deposition

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Si Eun Kim ◽  
Byungju Lee ◽  
Hyemin Jang ◽  
Juhee Chin ◽  
Ching Soong Khoo ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Neuropsychological Tests ◽  
Mixed Effects ◽  
Amnestic Mild Cognitive Impairment ◽  
Emission Tomography ◽  
Amyloid Pet ◽  
Cognitive Level ◽  
Visual Rating ◽  
Positron Emission ◽  
The Brain

Abstract Background The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition. Methods We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer’s disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1–9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group. Results Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7–9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1–3 or 4–6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex. Conclusions When predicting cognitive decline of patients with focal Aß deposition, the patients’ cognitive level, extent, and location of the focal involvement are important.

scholarly journals Flexibility as a marker of early cognitive decline in humanized apolipoprotein E ε4 (ApoE4) mice

2021 ◽  
Vol 102 ◽  
pp. 129-138
Author(s):  
Julien Schmitt ◽  
Anne-Lise Paradis ◽  
Mathieu Boucher ◽  
Laurent Andrieu ◽  
Pascal Barnéoud ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Apolipoprotein E

scholarly journals The Role of Vitamin D as a Biomarker in Alzheimer’s Disease

2021 ◽  
Vol 11 (3) ◽  
pp. 334
Author(s):  
Giulia Bivona ◽  
Bruna Lo Sasso ◽  
Caterina Maria Gambino ◽  
Rosaria Vincenza Giglio ◽  
Concetta Scazzone ◽  
...  
Keyword(s):  
Vitamin D ◽  
Risk Factor ◽  
Cognitive Decline ◽  
Immune Cell ◽  
Response To Treatment ◽  
Cellular Processes ◽  
Vitamin D Levels ◽  
The Brain ◽  
Key Questions

Vitamin D and cognition is a popular association, which led to a remarkable body of literature data in the past 50 years. The brain can synthesize, catabolize, and receive Vitamin D, which has been proved to regulate many cellular processes in neurons and microglia. Vitamin D helps synaptic plasticity and neurotransmission in dopaminergic neural circuits and exerts anti-inflammatory and neuroprotective activities within the brain by reducing the synthesis of pro-inflammatory cytokines and the oxidative stress load. Further, Vitamin D action in the brain has been related to the clearance of amyloid plaques, which represent a feature of Alzheimer Disease (AD), by the immune cell. Based on these considerations, many studies have investigated the role of circulating Vitamin D levels in patients affected by a cognitive decline to assess Vitamin D’s eventual role as a biomarker or a risk factor in AD. An association between low Vitamin D levels and the onset and progression of AD has been reported, and some interventional studies to evaluate the role of Vitamin D in preventing AD onset have been performed. However, many pitfalls affected the studies available, including substantial discrepancies in the methods used and the lack of standardized data. Despite many studies, it remains unclear whether Vitamin D can have a role in cognitive decline and AD. This narrative review aims to answer two key questions: whether Vitamin D can be used as a reliable tool for diagnosing, predicting prognosis and response to treatment in AD patients, and whether it is a modifiable risk factor for preventing AD onset.

Sign in / Sign up

Export Citation Format

Share Document