Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers

Background: It remains unclear how demographic and clinical characteristics are related to the risk of incident mild cognitive impairment (MCI) by its subtypes. Moreover, the contribution of the subtypes of incident MCI to the progression to dementia remains puzzling. Methods: We used data collected by the National Alzheimer Coordinating Center. Our analysis sample included cognitively normal subjects at baseline. The associations were examined using competing-risks survival regression models and Cox proportional hazards models. Results: About 16.3% of subjects developed incident MCI of whom 15.8% progressed to Alzheimer disease (overall mean follow-up of 4.3 years). The risk of incident amnestic MCI (aMCI) was greater in subjects with 1 copy (subhazard ratio [SHR]: 1.23; 95% CI: 1.00–1.50) or 2 copies (SHR: 2.14; 95% CI: 1.49–3.05) of the APOE ε4 allele than in those who had no ε4 allele. Multiple-domain aMCI patients were more likely to progress to dementia than single-domain aMCI patients (hazard ratio: 2.14; 95% CI: 1.28–3.58). Conclusions: Cognitively normal subjects with an APOE ε4 allele had a higher likelihood of developing aMCI and the MCI subtype was associated with the dementia subtype. Our findings provide important information about practical indicators for the prediction of cognitive decline.

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Differential effects of the interaction between the education and APOE ε4 allele on amyloid-beta retention and memory performances in cognitively normal older adults and Alzheimer's disease patients

Current Alzheimer Research ◽

10.2174/1567205017666201229113416 ◽

2020 ◽

Vol 17 ◽

Author(s):

Dong Woo Kang ◽

Sheng-Min Wang ◽

Hae-Ran Na ◽

Chang Uk Lee ◽

In-Ho Baek ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Test Scores ◽

Memory Performance ◽

Memory Function ◽

Neuropsychological Test ◽

Cognitively Normal ◽

Apoe Ε4 ◽

Two Factors ◽

Ε4 Allele

Background: Despite the effect of education and APOE ε4 allele on amyloid-beta (Aβ) retention and memory, previous studies have not dealt with an interaction between two factors on Aβ deposition and memory function in the course of Alzheimer’s disease (AD). Objective: To evaluate education by APOE ε4 allele interactions for Aβ retention and neuropsychological test scores in cognitively normal older adults without Aβ deposition [CN(Aβ-), n=45] and Alzheimer’s disease patients with Aβ retention [AD(Aβ+), n=33]. Methods: Multiple regression analyses (adjusted for age, gender) were conducted to examine the effects of education, APOE ε4 allele, and the interaction between the two factors on global, regional Aβ load quantified using [18F]flutemetamol standardized uptake value ratio with the pons as a reference region, and on neuropsychological test scores in each group. Results: The interaction between education and APOE ε4 allele had an effect on amyloid load in parietal lobes (uncorrected p < 0.05) and striatum (Bonferroni corrected p < 0.05) in each CN(Aβ-) and AD(Aβ+). There was also an interaction effect of education and APOE ε4 allele on the memory performance in each CN(Aβ-) and AD(Aβ+) (uncorrected p < 0.05). APOE ε4 carriers of both groups showed opposing slopes with each other in the correlation between the education years and Aβ load, memory performance. Conclusions: The current results suggest a possible explanation of the differential effects of education and APOE ε4 allele interactions on AD pathology and memory function at the beginning and end of AD progress. However, further study with a validating cohort is needed for confirming this explanation.

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APOE-ε4 allele load modifies the brain aging process in cognitively normal late middle aged and older adults

Proceedings of the International Conference on Artificial Intelligence, Information Processing and Cloud Computing - AIIPCC '19 ◽

10.1145/3371425.3371460 ◽

2019 ◽

Author(s):

Lan Lin ◽

Yuchao Wu ◽

Xuetao Wu ◽

Shuicai Wu

Keyword(s):

Older Adults ◽

Aging Process ◽

Brain Aging ◽

Middle Aged ◽

Cognitively Normal ◽

Apoe Ε4 ◽

Ε4 Allele ◽

The Brain

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APOE ε4 Carriers Have a Greater Propensity to Glycation and sRAGE Which Is Further Influenced by RAGE G82S Polymorphism

The Journals of Gerontology Series A ◽

10.1093/gerona/glz259 ◽

2019 ◽

Vol 75 (10) ◽

pp. 1899-1905 ◽

Cited By ~ 4

Author(s):

Permal Deo ◽

Varinderpal S Dhillon ◽

Ann Chua ◽

Philip Thomas ◽

Michael Fenech

Keyword(s):

Plasma Cholesterol ◽

High Plasma ◽

Advanced Glycation ◽

Cognitively Normal ◽

Apoe Ε4 ◽

Established Risk Factor ◽

Normal Individuals ◽

Glycation End Products ◽

Ε4 Allele ◽

The Common

Abstract APOE ε4 allele is an established risk factor for Alzheimer’s disease and hypercholesterolemia. However, its association with metabolic and genetic risk factors related to glycation is not clear. We tested the hypothesis that, apart from high plasma cholesterol, APOE ε4 carriers may also have higher advanced glycation end products (AGEs) and total soluble extracellular domain of RAGE (sRAGE) and that these biomarkers may be modified by the common Gly82Ser (G82S) polymorphism (rs2070600) in the RAGE gene. To test this, we measured these biomarkers in 172 healthy cognitively normal individuals, of which 32 were APOE ε4 carriers and 140 noncarriers. APOE ε4 carriers showed higher levels of cholesterol (p < .001), glyoxal (p < .001), fluorescent AGEs (p < .001), Nε-carboxymethyllysine (p < .001) and sRAGE (p = .018) when compared to noncarriers. Furthermore, sRAGE was also higher in those that did not carry the A allele of the RAGE gene that codes for serine instead of glycine (p = .034). Our study indicates that APOE ε4 carriers have a greater propensity to glycation than noncarriers which may further increase their risk for diabetes and dementia. The increased sRAGE levels in APOE ε4 carriers suggests a defensive response against AGEs that may be further influenced by the RAGE G82S polymorphism.

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Effects of amyloid pathology and the APOE ε4 allele on the association between cerebrospinal fluid Aβ38 and Aβ40 and brain morphology in cognitively normal 70-years-olds

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2020.10.033 ◽

2021 ◽

Vol 101 ◽

pp. 1-12

Author(s):

Olof Lindberg ◽

Silke Kern ◽

Johan Skoog ◽

Alejandra Machado ◽

Joana B. Pereira ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Brain Morphology ◽

Cognitively Normal ◽

Amyloid Pathology ◽

Apoe Ε4 ◽

Ε4 Allele

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Molecular Genetics of Early- and Late-Onset Alzheimer’s Disease

Current Gene Therapy ◽

10.2174/1566523220666201123112822 ◽

2020 ◽

Vol 20 ◽

Author(s):

Md. Sahab Uddin ◽

Sharifa Hasana ◽

Md. Farhad Hossain ◽

Md. Siddiqul Islam ◽

Tapan Behl ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Massively Parallel Sequencing ◽

Late Onset ◽

Current Knowledge ◽

The Elderly ◽

Apoe Ε4 ◽

Sequencing Technologies ◽

Genetic Components ◽

Ε4 Allele

: Alzheimer’s disease (AD) is the most common form of dementia in the elderly and this complex disorder is associated with environmental as well as genetic components. Early-onset AD (EOAD) and late-onset AD (LOAD, more common) are major identified types of AD. The genetics of EOAD is extensively understood with three genes variants such as APP, PSEN1, and PSEN2 leading to disease. On the other hand, some common alleles including APOE are effectively associated with LOAD identified but the genetics of LOAD is not clear to date. It has been accounted that about 5% to 10% of EOAD patients can be explained through mutations in the three familiar genes of EOAD. The APOE ε4 allele augmented the severity of EOAD risk in carriers, and APOE ε4 allele was considered as a hallmark of EOAD. A great number of EOAD patients, who are not genetically explained, indicate that it is not possible to identify disease- triggering genes yet. Although several genes have been identified through using the technology of next-generation sequencing in EOAD families including SORL1, TYROBP, and NOTCH3. A number of TYROBP variants were identified through exome sequencing in EOAD patients and these TYROBP variants may increase the pathogenesis of EOAD. The existence of ε4 allele is responsible for increasing the severity of EOAD. However, several ε4 allele carriers live into their 90s that propose the presence of other LOAD genetic as well as environmental risk factors that are not identified yet. It is urgent to find out missing genetics of EOAD and LOAD etiology to discover new potential genetics facets which will assist to understand the pathological mechanism of AD. These investigations should contribute to developing a new therapeutic candidate for alleviating, reversing and preventing AD. This article based on current knowledge represents the overview of the susceptible genes of EOAD, and LOAD. Next, we represent the probable molecular mechanism which might elucidate the genetic etiology of AD and highlight the role of massively parallel sequencing technologies for novel gene discoveries.

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