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.

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.

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.

DIET, CHOLESTEROL METABOLISM, AND ALZHEIMER'S DISEASE: APOLIPOPROTEIN E AS A POSSIBLE LINK?

2006 ◽  
Vol 54 (12) ◽  
pp. 1963-1965 ◽  
Author(s):  
Francesco Panza ◽  
Cristiano Capurso ◽  
Alessia D'Introno ◽  
Anna M. Colacicco ◽  
Angelo Del Parigi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Cholesterol Metabolism

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.

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

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.

Total Cholesterol and APOE-Related Risk for Alzheimer’s Disease in the Alzheimer’s Disease Neuroimaging Initiative

2021 ◽  
pp. 1-10
Author(s):  
Michelle M. Dunk ◽  
Ira Driscoll ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Total Cholesterol ◽  
Cholesterol Metabolism ◽  
Apoe Genotype ◽  
Control Group ◽  
Cholesterol Levels ◽  
Related Risk ◽  
E4 Allele

Background: APOE ɛ4 allele confers greatest genetic risk for Alzheimer’s disease (AD), yet mechanisms underlying this risk remain elusive. APOE is involved in lipid metabolism, and literature suggest relationships between high total cholesterol, APOE, and AD. Further investigation is needed to elucidate the potential role of total cholesterol in AD risk. Objective: To investigate the relationship between total cholesterol and APOE-related AD risk in the Alzheimer’s Disease Neuroimaging Initiative. Methods: Participants (N = 1,534) were classified as controls (cognitively normal; N = 404), early mild cognitive impairment (MCI; N = 294), late MCI (N = 539), or AD (N = 297). Total cholesterol levels were compared across APOE genotype and diagnosis. Mendelian randomization was performed to examine causality between total cholesterol and AD risk using APOE as a genetic instrument. Results: Total cholesterol was higher in APOE4+ compared to APOE3 and APOE2+ (ps < 0.04) carriers. Those with AD and late MCI (ps < 0.001) had higher total cholesterol than the control group. Comparing APOE4+ to APOE3 carriers, the predicted odds ratios per mg/dL greater total cholesterol were 1.11 for MCI (95% confidence interval, 1.04–7.32), 1.05 for early MCI (1.01–3.22), 1.13 for late MCI (1.05–11.70), 1.21 for AD (1.09–54.05), and 1.13 for composite dementia (MCI or AD; 1.06–11.59) (ps < 0.05, F-statistics>10). Conclusion: Higher total cholesterol may be a significant contributor to AD risk, particularly in APOE4 carriers who, based on existing literature, tend to have impaired cholesterol metabolism. Our findings highlight a possible mechanism by which APOE confers AD risk and indicate potential for AD risk modification through maintenance of healthy total cholesterol levels.

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.)

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