Inheritance of the ApoE ε4 Allele Increases the Rate of Brain Atrophy in Dementia Patients

1999 ◽  
Vol 10 (4) ◽  
pp. 262-268 ◽  
Author(s):  
Lars-Olof Wahlund ◽  
Per Julin ◽  
Lars Lannfelt ◽  
Johan Lindqvist ◽  
Leif Svensson
Keyword(s):  
Brain Atrophy ◽  
Apoe Ε4 ◽  
Dementia Patients ◽  
Ε4 Allele

APOE ε4 Allele Status in Korean Dementia Patients with Severe White Matter Hyperintensities

2011 ◽  
Vol 24 (3) ◽  
pp. 519-524 ◽  
Author(s):  
Yun Jeong Hong ◽  
Bora Yoon ◽  
Yong S. Shim ◽  
A-Hyun Cho ◽  
Hae-Eun Shin ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Apoe Ε4 ◽  
Dementia Patients ◽  
Allele Status ◽  
Ε4 Allele

Interaction with the MAPT H1H1 Genotype Increases Dementia Risk in APOE ε4 Carriers in a Population of Southern India

2016 ◽  
Vol 42 (5-6) ◽  
pp. 255-264 ◽  
Author(s):  
P.S. Jairani ◽  
P.M. Aswathy ◽  
Srinivas Gopala ◽  
Joe Verghese ◽  
P.S. Mathuranath
Keyword(s):  
Disease Risk ◽  
Strong Association ◽  
Multivariate Logistic Regression Analysis ◽  
Lewy Bodies ◽  
Southern India ◽  
Control Group ◽  
Apoe Ε4 ◽  
Dementia Patients ◽  
Dementia Risk ◽  
Ε4 Allele

Background: This study delineates the role of the interaction of apolipoprotein E (APOE) and MAPT alleles in contributing to disease risks of dementia in a southern Indian population. Methods: A sample of 419 patients comprising Alzheimer's disease (AD; n = 156), mild cognitive impairment (MCI; n = 87), frontotemporal dementia (FTD; n = 127), vascular dementia (VD; n = 37), and dementia with Lewy bodies (DLB; n = 12) was analysed in comparison with a control group (n = 138). APOE genotyping and MAPT haplotyping were performed on all study subjects. Results: Multivariate logistic regression analysis showed that variability on the APOE locus influenced the relative risk of dementia in the study population. The APOE ε4 allele increased the disease risk most significantly for AD (OR = 3.468, p < 0.0001) and MCI (OR = 2.901, p < 0.0001). The APOE ε2 allele remained protective for AD (OR = 0.205, p < 0.05). For FTD, VD, and DLB, the APOE ε4 allele was ineffectual in modulating disease risk. The MAPT H1 haplotype was not an overrepresented marker of neurodegenerative diseases. The H1H1 genotype had an additive effect in contributing to either disease risk in combination with the APOE ε4 allele or protection in combination with the APOE ε2 or ε3 allele. Conclusions: This study is a reappraisal of the strong association of APOE variability with AD in southern India when compared to other dementia groups, while the transcriptional differences between MAPT haplotypes have a limited role in Indian dementia patients.

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

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.

scholarly journals Disruption of Arterial Perivascular Drainage of Amyloid-β from the Brains of Mice Expressing the Human APOE ε4 Allele

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41636 ◽  
Author(s):  
Cheryl A. Hawkes ◽  
Patrick M. Sullivan ◽  
Sarah Hands ◽  
Roy O. Weller ◽  
James A. R. Nicoll ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Human Apoe ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Perivascular Drainage

scholarly journals Decline in verbal memory during preclinical Alzheimer's disease: Examination of the effect of APOE genotype

2002 ◽  
Vol 8 (7) ◽  
pp. 943-955 ◽  
Author(s):  
KELLY L. LANGE ◽  
MARK W. BONDI ◽  
DAVID P. SALMON ◽  
DOUGLAS GALASKO ◽  
DEAN C. DELIS ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Episodic Memory ◽  
Verbal Memory ◽  
Verbal Learning ◽  
Apoe Genotype ◽  
Apoe Ε4 ◽  
Dementia Syndrome ◽  
Ε4 Allele

A subtle decline in episodic memory often occurs prior to the emergence of the full dementia syndrome in nondemented older adults who develop Alzheimer's disease (AD). The APOE-ε4 genotype may engender a more virulent form of AD that hastens this decline. To examine this possibility, we compared the rate of decline in episodic memory during the preclinical phase of AD in individuals with or without at least one APOE ε4 allele. Nondemented normal control (NC; n = 84) participants, nondemented older adults who subsequently developed dementia within 1 or 2 years (i.e., preclinical AD; n = 20), and patients with mild AD (n = 53) were examined with 2 commonly employed tests of episodic memory, the Logical Memory subtest of the Wechsler Memory Scale–Revised and the California Verbal Learning Test. Results revealed a precipitous decline in verbal memory abilities 1 to 2 years prior to the onset of the dementia syndrome, but there was little effect of APOE genotype on the rate of this memory decline. The presence of an APOE-ε4 allele, however, did have a differential effect on the sensitivity of the 2 types of memory tests for tracking progression and made an independent contribution to the prediction of conversion to AD. (JINS, 2002, 8, 943–955.)

P4-189: Effect of the APOE-ε4 allele on longitudinal changes in cortical thickness in normal aging

2012 ◽  
Vol 8 (4S_Part_19) ◽  
pp. P702-P703
Author(s):  
Tara Madhyastha ◽  
Paul Borghesani ◽  
Elizabeth Aylward ◽  
Monique Cherrier ◽  
Katie Askren ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
Normal Aging ◽  
Longitudinal Changes ◽  
Apoe Ε4 ◽  
Ε4 Allele

Interplay between the APOE Genotype and Possible Plasma Biomarkers in Alzheimer’s Disease

2018 ◽  
Vol 15 (10) ◽  
pp. 938-950 ◽  
Author(s):  
Martina Zverova ◽  
Eva Kitzlerova ◽  
Zdenek Fisar ◽  
Roman Jirak ◽  
Jana Hroudova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Apoe Genotype ◽  
Plasma Biomarkers ◽  
Plasma Melatonin ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Severity Of Dementia

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders. Objective: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD. Method: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls. Results: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in patients with AD compared to those in controls, independent of the presence of comorbid depressive symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence of depression or the severity of dementia in AD. Conclusion: Our findings indicate the existence of a little-known specific APOE-mediated mechanism that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the APOE ε4 allele.

scholarly journals APOE-ε4 polymorphism and cognitive deficit among the elderly population of Fernando de Noronha

2008 ◽  
Vol 66 (2b) ◽  
pp. 298-302 ◽  
Author(s):  
Anália Nusya Garcia ◽  
Helker Albuquerque da Silva ◽  
Renan Carlos Silva ◽  
Eliane Maria Medeiros Leal ◽  
Lorena Rodrigues ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Elderly Population ◽  
Cognitive Deficit ◽  
The Elderly ◽  
Clock Drawing Test ◽  
Apoe Ε4 ◽  
Pcr Rflp ◽  
Fernando De Noronha ◽  
Ε4 Allele

BACKGROUND: Polymorphism of the gene for apolipoprotein E (APOE) is an important risk factor for the development of Alzheimer's disease. The ε4 allele of the APOE gene has been linked with a number of neuropsychiatric illnesses, and also with stress and depression among geriatric populations. OBJECTIVE: To identify APOE-ε4 polymorphism and correlate this with cognitive deficit among the elderly population of the island of Fernando de Noronha. METHOD: Neuropsychiatric tests (mini-mental state examination, verbal fluency test and clock drawing test) were applied to 52 elderly people without Alzheimer's disease. DNA was isolated from peripheral blood and genotyping of APOE was done by the PCR-RFLP method. RESULTS: 87% of the elderly population (mean age 69.6±7.0) had cognitive deficit. CONCLUSION: The observed frequency of the ε4 allele was 10%, but the correlation between the presence of ε4 and cognitive deficit in this population was not statistically significant.

scholarly journals Total ApoE and ApoE4 Isoform Assays in an Alzheimer's Disease Case-control Study by Targeted Mass Spectrometry (n = 669): A Pilot Assay for Methionine-containing Proteotypic Peptides

2012 ◽  
Vol 11 (11) ◽  
pp. 1389-1403 ◽  
Author(s):  
Romain Simon ◽  
Marion Girod ◽  
Catherine Fonbonne ◽  
Arnaud Salvador ◽  
Yohann Clément ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Case Control Study ◽  
Case Control ◽  
Performic Acid ◽  
Protein Levels ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Control Study

Allelic polymorphism of the apolipoprotein E (ApoE) gene (ApoE ε2, ApoE ε3 and ApoE ε4 alleles) gives rise to three protein isoforms (ApoE2, ApoE3 and ApoE4) that differ by 1 or 2 amino acids. Inheritance of the ApoE ε4 allele is a risk factor for developing Alzheimer's disease (AD). The potential diagnostic value of ApoE protein levels in biological fluids (i.e. cerebrospinal fluid, plasma and serum) for distinguishing between AD patients and healthy elderly subjects is subject to great controversy. Although a recent study reported subnormal total ApoE and ApoE4 levels in the plasma of AD patients, other studies have found normal or even elevated protein levels (versus controls). Because all previously reported assays were based on immunoenzymatic techniques, we decided to develop an orthogonal assay based on targeted mass spectrometry by tracking (i) a proteotypic peptide common to all ApoE isoforms and (ii) a peptide that is specific for the ε4 allele. After trypsin digestion, the ApoE4-specific peptide contains an oxidation-prone methionine residue. The endogenous methionine oxidation level was evaluated in a small cohort (n = 68) of heterozygous ε3ε4 carriers containing both healthy controls and AD patients. As expected, the proportion of oxidized residues varied from 0 to 10%, with an average of 5%. We therefore developed a standardized strategy for the unbiased, absolute quantification of ApoE4, based on performic acid oxidization of methionine. Once the sample workflow had been thoroughly validated, it was applied to the concomitant quantification of total ApoE and ApoE4 isoform in a large case-control study (n = 669). The final measurements were consistent with most previously reported ApoE concentration values and confirm the influence of the different alleles on the protein expression level. Our results illustrate (i) the reliability of selected reaction monitoring-based assays and (ii) the value of the oxidization step for unbiased monitoring of methionine-containing proteotypic peptides. Furthermore, a statistical analysis indicated that neither total ApoE and ApoE4 levels nor the ApoE/ApoE4 ratio correlated with the diagnosis of AD. These findings reinforce the conclusions of previous studies in which plasma ApoE levels had no obvious clinical significance.

scholarly journals Association between APOE ε4 Allele and Vascular Dementia: The Cache County Study

2010 ◽  
Vol 29 (3) ◽  
pp. 248-253 ◽  
Author(s):  
Yi-Fang Chuang ◽  
Kathleen M. Hayden ◽  
Maria C. Norton ◽  
JoAnn Tschanz ◽  
John C.S. Breitner ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Cache County
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