Interaction Between APOE Genotype and Diabetes in Longevity

2021 ◽  
pp. 1-8
Author(s):  
Mitsuru Shinohara ◽  
Kaoru Suzuki ◽  
Guojun Bu ◽  
Naoyuki Sato
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Interactive Effect ◽  
Apoe Genotype ◽  
Potential Interaction ◽  
Cognitive Status ◽  
Diabetic Status ◽  
Clinical Records ◽  
Harmful Effects

Background: While both apolipoprotein E (APOE) genotype and diabetes affect longevity as well as Alzheimer’s disease, their relationship remains to be elucidated. Objective: The current study investigated the potential interaction between diabetes and APOE for lifespan and their relationship with cognitive status. Methods: We reviewed the National Alzheimer’s Coordinating Center (NACC) dataset, which documents longitudinally clinical records of 24,967 individuals with APOE genotype and diabetic status. Results: Diabetes was associated with shorter lifespan in APOE3 carriers (n = 12,415, HR = 1.29, 95%CI = 1.17–1.42, p <  0.001) and APOE2 carriers (n = 2,390, HR = 1.37, 95%CI = 1.10–1.69, p = 0.016), while such associations were weaker and not significant in APOE4 carriers (n = 9,490, HR = 1.11, 95%CI = 0.99–1.24, p = 0.162). As there is a significant interactive effect of cognitive status and diabetes on lifespan (p <  0.001), we stratified subjects by cognitive status and observed persistent APOE-dependent harmful effects of diabetes in nondemented individuals but not demented individuals. Notably, questionnaire-based activity status, with which we previously observed an association between APOE genotype and longevity, was also significantly affected by diabetes only in non-APOE4 carriers. Conclusion: The effects of diabetes on longevity vary among APOE genotype. These effects are observed in nondemented individuals and are potentially associated with activity status during their lifespan.

scholarly journals Associations between depression, sleep disturbance, and apolipoprotein E in the development of Alzheimer's disease: dementia

2016 ◽  
Vol 28 (9) ◽  
pp. 1409-1424 ◽  
Author(s):  
Shanna L. Burke ◽  
Peter Maramaldi ◽  
Tamara Cadet ◽  
Walter Kukull
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Sleep Disturbance ◽  
Reference Group ◽  
Synergistic Effects ◽  
Apoe Genotype ◽  
The Elderly ◽  
Prodromal Symptom ◽  
Apoe Genotypes

ABSTRACTBackground:Alzheimer's disease (AD) is a neurodegenerative brain disease that causes cognitive impairment and dementia. Within the US, AD is the most common form of dementia in the elderly, affecting 1 in 10 people over the age of 65. Sleep disturbance has been called a “public health epidemic” and, like depression, is a prodromal symptom of AD but may also contribute to the risk of developing AD. It was hypothesized that sleep disturbance, depression, and the apolipoprotein E (APOE) genotype increase the likelihood of AD.Methods:Utilizing data from the National Alzheimer's Coordinating Center, information from evaluations of 11,453 cognitively asymptomatic participants was analyzed. Survival analysis was used to explore the independent relationships between depression, sleep disturbance, and APOE genotypes with eventual AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic effects of psychosocial factors as moderated by APOE genotypes.Results:This study reinforced the association between APOE and AD. The hazard of developing AD was eight times higher for those with recent depression and the Ɛ4 homozygote (HR = 8.15 [3.70–17.95]). Among Ɛ4 carriers with clinician-verified depression, the hazard was ten times that of the reference group (HR = 10.11 [4.43–23.09]). The hazard for Ɛ4 carriers reporting sleep disturbance was almost 7 times greater than the reference group (HR = 6.79 [2.38–19.37]).Conclusion:Findings suggest that sleep disturbance, depression, and APOE Ɛ4 genotype are associated with AD during follow-up evaluations among a group of initially cognitively asymptomatic participants. This study contributes to the literature base exploring an increased hazard or risk of AD due to potential modifiable risk factors as well as genetic biomarkers, such as APOE.

scholarly journals Apolipoprotein E and the CNS Response to Injury

1998 ◽  
Vol 18 (5) ◽  
pp. 465-471 ◽  
Author(s):  
Daniel T. Laskowitz ◽  
Karen Horsburgh ◽  
Allen D. Roses
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Cholesterol Metabolism ◽  
Apoe Genotype ◽  
Acute Injury ◽  
Multifunctional Protein ◽  
Clinical Observations ◽  
Injured Brain ◽  
Antioxidant Effects

Apolipoprotein E (apoE) is a multifunctional protein with an expanding role in the neurobiology of disease. Although originally described in the context of cholesterol metabolism, interest in the neurobiology of apoE has intensified following the association between apoE genotype and risk of developing Alzheimer's disease. Recent clinical observations also suggest that apoE genotype may influence recovery after a variety of neurological insults. Thus, in addition to the study of disease-specific mechanisms by which apoE may modulate susceptibility of developing Alzheimer's disease, there has been an increasing focus on its role in modulating the CNS response to acute injury. Although the neurobiology of apoE in the injured brain remains incompletely defined, there is evidence to suggest neurotrophic, immunomodulatory, and antioxidant effects.

scholarly journals Plasma Lipocalin 2 in Alzheimer’s disease: potential utility in the differential diagnosis and relationship with other biomarkers

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Peter Hermann ◽  
Anna Villar-Piqué ◽  
Matthias Schmitz ◽  
Christian Schmidt ◽  
Daniela Varges ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Apoe Genotype ◽  
Cognitive Status ◽  
Differential Diagnoses ◽  
Study Cohort ◽  
Healthy Controls ◽  
Lipocalin 2 ◽  
Reactive Microglia

Abstract Background Lipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer’s disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer’s disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer’s disease, differential diagnoses, other biomarkers, and clinical data. Methods For this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer’s disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer’s disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28). Results Plasma Lipocalin-2 was significantly lower in Alzheimer’s disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer’s pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer’s disease and healthy controls were 0.783 (95%CI: 0.712–0.855) in the study cohort and 0.766 (95%CI: 0.627–0.905) in the validation cohort. The area under the curve for Alzheimer’s disease versus vascular dementia was 0.778 (95%CI: 0.667–0.890) in the study cohort. In Alzheimer’s disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with non-rapidly progressive Alzheimer’s disease (p = 0.013). Conclusions Plasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer’s disease and seems to be independent from currently employed biomarkers.

Apolipoprotein E Genotype and its Effect on Duration and Severity of Early and Late Onset Alzheimer's Disease

1995 ◽  
Vol 167 (4) ◽  
pp. 533-536 ◽  
Author(s):  
Jennie Norrman ◽  
Anthony J. Brookes ◽  
Celia Yates ◽  
David St Clair
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Apoe Genotype ◽  
Increased Risk ◽  
Apolipoprotein E Genotype

BackgroundThe apolipoprotein E (ApoE) ∊4 allele is associated with an increased risk of senile and probably presenile Alzheimer's disease. It is not yet clear whether the ∊4 allele also influences the duration/rate of progress of illness and the severity of the dementia.MethodWe have retrospectively examined a series of ApoE genotyped presenile and senile autopsy cases of Alzheimer's disease (AD) for length of illness and severity of pathology.ResultsWe find no evidence that ApoE genotype affects the rate of progress of AD, but the degree of pathology at death may be increased.ConclusionIt appears that the rate of progress of AD as a whole is independent of the ApoE genotype.

Apolipoprotein E and Alzheimer's disease: signal transduction mechanisms

2001 ◽  
Vol 67 ◽  
pp. 101-109 ◽  
Author(s):  
Warren J. Strittmatter
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Cholesterol Metabolism ◽  
Scavenger Receptor ◽  
Apoe Genotype ◽  
Density Lipoprotein ◽  
Cell Trafficking ◽  
Pathophysiological Mechanism ◽  
Apoe Receptors

The three common apolipoprotein E (ApoE) alleles differentially contribute to the risk of Alzheimer's disease (AD). While the APOE genotype alters susceptibility to disease expression, individuals with APOE ϵ4 alleles have the highest risk of developing AD; the APOE ϵ4 allele is neither essential nor sufficient on its own to cause AD. Since the discovery, in 1992, of the involvement of APOE in AD, many scientists have explored the role of the ApoE isoforms in the central nervous system in an effort to elucidate their roles in the pathophysiological mechanism of this disease. While many hypotheses have been proposed, none has been proven. ApoE was discovered through investigations into cholesterol metabolism. In serum and in cerebrospinal fluid ApoE binds lipoprotein particles, which contain cholesterol esters, and is critical in the shuttling of cholesterol from cell to cell. Trafficking of ApoE is mediated by specific interactions with cell-surface receptors. As described later, several families of ApoE receptors with diverse functions have been discovered. The roles of these receptors are proving increasingly complex since additional interactions with other ligands and with other intracellular proteins are rapidly being identified. It was once thought that these receptors only shuttle ApoE-containing phospholipid particles from the extracellular environment into the cell, but they also transduce a number of additional intracellular signals and interactions. Molecular signalling cascades initiated by the various ApoE receptors modulate a number of critical cellular processes. To date, two functional classes of ApoE receptors have been identified. The first is the low-density lipoprotein receptor family and the second the scavenger receptor families.

Inconstant apolipoprotein E (ApoE)-like immunoreactivity in amyloid β protein deposits: relationship with APOE genotype in aging brain and Alzheimer's disease

1996 ◽  
Vol 92 (2) ◽  
pp. 180-185 ◽  
Author(s):  
Toshiki Uchihara ◽  
C. Duyckaerts ◽  
Françoise Lazarini ◽  
Karima Mokhtari ◽  
Danielle Seilhean ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Apoe Genotype ◽  
Amyloid Β ◽  
Aging Brain ◽  
Amyloid Β Protein ◽  
Protein Deposits ◽  
Β Protein

P4-354: Baseline CSF BETA-AMYLOID 42 correlates with ApoE genotype and baseline cognitive status in a phase II avagacestat predementia Alzheimer's disease study

2012 ◽  
Vol 8 (4S_Part_21) ◽  
pp. S782-S782
Author(s):  
Holly Soares ◽  
Flora Berisha ◽  
Carol Gleason ◽  
George Green ◽  
Jane Tiller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Phase Ii ◽  
Apoe Genotype ◽  
Beta Amyloid ◽  
Cognitive Status ◽  
Disease Study

Cognitive asymmetries associated with apolipoprotein E genotype in patients with Alzheimer's disease

2003 ◽  
Vol 9 (5) ◽  
pp. 751-759 ◽  
Author(s):  
MICHAEL J. FINTON ◽  
JOHN A. LUCAS ◽  
JULIE D. RIPPETH ◽  
DARYL L. BOHAC ◽  
GLENN E. SMITH ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Cognitive Performance ◽  
Cognitive Abilities ◽  
Apoe Genotype ◽  
Unique Contribution ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
The Relationship

The relationship between apolipoprotein E (apoE) genotype and cognitive performance was examined in 200 patients with probable Alzheimer's disease (AD). Differences between composite measures of verbal and nonverbal functioning were used to define asymmetric patterns of cognition. Patients who were homozygous for apoE ε4 demonstrated relatively worse nonverbal as compared to verbal cognitive ability. In contrast, participants who were heterozygous for apoE ε4 or who possessed no ε4 allele demonstrated relatively equivalent verbal and nonverbal cognitive abilities. Although age and dementia severity also contributed to these patterns, apoE genotype appears to have a significant unique contribution to cognitive performance in these individuals. The ε4 allele may thus be associated with a specific neurocognitive phenotype among patients with AD, with the overall pattern of cognitive asymmetry dependent upon ε4 dose. (JINS, 2003, 9, 751–759.)

Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

2018 ◽  
Vol 18 (4) ◽  
pp. 216-224 ◽  
Author(s):  
Anthoula C. Tsolaki ◽  
Olympia Gatzima ◽  
Makrina Daniilidou ◽  
Eutuxia Lazarou ◽  
Panagiotis D. Bamidis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Apoe Genotype ◽  
Dependent Manner ◽  
Apoe Ε4 ◽  
Healthy Elderly ◽  
Increased Risk

Background: Apolipoprotein E ε4 allele (APOEε4) is a major genetic risk factor for Alzheimer’s disease (AD). APOEε4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. Methods: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA). Descriptive statistics, one-way analysis of variance with Bonferroni post hoc tests, Pearson chi-square test, and binary logistic regression models were used for the statistical analysis. Results: The APOE genotype and allele frequencies in AD group were significantly different from those in the Control and MCI groups. The frequencies of ε4/4 homozygotes were 1.9, 1.6, and 5.7%, while the ε4/– carriers’ distribution was 22.5, 24.1, and 37.4% in the Control, MCI, and AD groups respectively. The estimated odds of ε4/4 for AD was 5.731-fold higher compared to the estimated odds of ε3/3. The interaction between gender and APOE did not have a significant effect on the odds for MCI (p = 0.942) and AD (p = 0.984). Conclusion: In Greece, APOE ε4 presence is related to an increased risk for AD in a dose-related manner. Contrary to long-standing views, men and women with the APOE ε4 genotype have nearly the same odds of developing MCI and AD.

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