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Apolipoprotein E And Alzheimer Disease: An Update On Genetic And Functional Analyses

A. Saunders
Published 2000 · Biology, Medicine

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Exceptional advances have been made in understanding the genetics of how common polymorphisms of the apolipoprotein E gene influence the risk and age of onset of Alzheimer disease (AD). The major genetic susceptibility locus for the common forms of AD, there are 3 common alleles, designated ε2, ε3, and ε4. The inheritance of each dose of APOE4 increases the risk of disease and decreases the age of onset; conversely, the APOE2 allele appears to be protective, by lowering the risk of disease and increasing the age of onset. Testing for the APOE4 allele can be a clinically useful tool in the early diagnosis of cognitively impaired patients suspected of having AD. The APOE4 allele also negatively influences functional recovery following a variety of brain insults. What remains in the study of apolipoprotein E is an explanation of how minor changes in a protein can produce such striking differences in risk and age of onset. In vitro and animal model studies strongly suggest that brain apolipoprotein E is a multifunctional molecule, with potential roles in amyloid deposition and clearance, microtubule stability, intracellular signaling, immune modulation, glucose metabolism, oxidative stress, and other cellular processes. While the relevance of these proposed functions to the etiology of AD remains a mystery, these and other hypotheses will be tested as the field of apoE neurobiology grows, adding relevant new data to the functions of apoE in health and in the pathogenic mechanisms leading to AD.
This paper references
10.1111/j.1471-4159.1987.tb02874.x
Cerebrospinal Fluid Proteins Studied by Two‐Dimensional Gel Electrophoresis and Immunoblotting Technique
F. Wiederkehr (1987)
10.1002/ANA.410230206
Clinical, pathological, and neurochemical changes in dementia: A subgroup with preserved mental status and numerous neocortical plaques
R. Katzman (1988)
10.1172/JCI115288
Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.
M. Linton (1991)
10.1016/0006-8993(91)91092-F
Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease
Y. Namba (1991)
10.1007/BF03324196
Molecular genetics of Alzheimer's disease.
S. Sorbi (1993)
10.1073/PNAS.90.5.1977
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
W. Strittmatter (1993)
10.1073/PNAS.90.20.9649
Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.
D. Schmechel (1993)
10.1126/SCIENCE.8346443
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.
E. Corder (1993)
Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease.
A. M. Saunders (1993)
10.1073/PNAS.90.17.8098
Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease.
W. Strittmatter (1993)
10.1146/ANNUREV.BI.63.070194.003125
Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP).
M. Krieger (1994)
10.1126/SCIENCE.8290965
Alzheimer's disease and possible gene interaction.
P. St George-Hyslop (1994)
Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease.
C. Harrington (1994)
10.1073/PNAS.91.23.11183
Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease.
W. Strittmatter (1994)
10.1038/NG0694-180
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
E. Corder (1994)
Apolipoprotein E allele epsilon 4 is linked to increased deposition of the amyloid beta-peptide (A-beta) in cases with or without Alzheimer's disease.
C. Berr (1994)
10.1161/01.CIR.90.1.1
NHLBI funding policies. Enhancing stability, predictability, and cost control.
C. Lenfant (1994)
10.1016/0304-3940(94)90204-6
Isoform-specific interactions of apolipoprotein E with the microtubule-associated protein MAP2c: implications for Alzheimer's disease
David Y. Huang (1994)
10.1212/WNL.44.10.1950
The apolipoprotein E allele epsi;4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease
D. Galasko (1994)
Isoform-specific binding of apolipoprotein E to beta-amyloid.
M. LaDu (1994)
10.1146/ANNUREV.BIOCHEM.63.1.601
Structures and Functions of Multiligand and Lipoprotein Receptors
M. Krieger (1994)
10.1006/MCPR.1994.1073
Apo E genotypes in multiple sclerosis, Parkinson's disease, schwannomas and late-onset Alzheimer's disease.
D. Rubinsztein (1994)
10.1016/S0065-3233(08)60642-7
Apolipoprotein E: structure-function relationships.
K. Weisgraber (1994)
10.1093/HMG/3.4.569
Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region.
M. C. Chartier-Harlin (1994)
10.1038/NG0594-74
Apolipoprotein E4 allele in a population–based study of early–onset Alzheimer's disease
C. Duijn (1994)
Apolipoprotein E: Structure–function relationship
KH Weisgraber (1994)
Apolipoprotein E allele frequency in patients with cognitive defects following cardiopulmonary bypass
B Tardiff (1994)
Structures and functions of multiligand lipoprotein receptors: Macrophage scavenger receptors and LDL receptorrelated protein (LRP)
M Krieger (1994)
Structure–function relationship
Kh Weisgraber (1994)
10.1016/0014-4886(95)90019-5
On the metabolism of apolipoprotein E and the Alzheimer diseases
A. Roses (1995)
10.1038/NM0295-135
Apolipoprotein E ε4 allele is associated with deposition of amyloid β-protein following head injury
J. Nicoll (1995)
10.1212/WNL.45.11.1985
Alzheimer's disease with and without coexisting Parkinson's disease changes
M. Gearing (1995)
10.1097/00005072-199511000-00010
Regional Variation in the Distribution of Apolipoprotein E and Aβ in Alzheimer's Disease
Marla Gearing (1995)
10.1038/NM0995-852
ApoE as a prognostic factor for post–traumatic coma
S. Sorbi (1995)
10.1074/JBC.270.34.19791
The Inhibitory Effect of Apolipoprotein E4 on Neurite Outgrowth Is Associated with Microtubule Depolymerization (*)
B. Nathan (1995)
10.1038/NM0795-603
Head injury, amyloid β and Alzheimer's disease
A. Roses (1995)
10.1016/S0140-6736(95)91411-0
ApoE genotype and survival from intracerebral haemorrhage
M. Alberts (1995)
10.1097/00001756-199511270-00025
Phosphorylation of tau protein is not affected in mice lacking apolipoprotein E.
L. Mercken (1995)
10.1016/0304-3940(95)12007-Q
Phosphorylation of tau in apolipoprotein E-deficient mice
I. Genis (1995)
10.1002/ANA.410380626
Apolipoprotein E genotyping in the diagnosis of alzheimer's disease
M. Ilyas kamboh (1995)
10.1001/JAMA.1995.03520360056039
Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease.
G. Small (1995)
10.1212/WNL.45.11.1991
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
C. Hulette (1995)
10.1006/exnr.1995.1088
Neurodegeneration in the Central Nervous System of apoE-Deficient Mice
E. Masliah (1995)
Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury.
J. Nicoll (1995)
10.1212/WNL.45.3.555
Synergistic Effects of Traumatic Head Injury and Apolipoprotein-epsilon4 in Patients With Alzheimer's Disease
R. Mayeux (1995)
10.1016/0304-3940(95)11649-H
ApoE3 binding to tau tandem repeat I is abolished by tau serine262 phosphorylation
David Y. Huang (1995)
10.1212/WNL.45.7.1323
Apolipoprotein E, survival in Alzheimer's disease patients, and the competing risks of death and Alzheimer's disease
E. Corder (1995)
10.1002/ANA.410380105
Apolipoprotein E genotyping in the differential diagnosis, not prediction, of Alzheimer's disease
A. Roses (1995)
Apolipoprotein E genotyping in differential diagnosis, not prediction, of Alzheimer’s disease (Point of View)
AD Roses (1995)
genotyping in differential diagnosis , not prediction , of Alzheimer ’ s disease ( Point of View )
AD Roses (1995)
Measuring the genetic contribution of APOE in late-onset Alzheimer diease
AD Roses (1995)
Apolipoprotein E genotyping in differential diagnosis, not prediction, of Alzheimer's disease (Point of View)
(1995)
10.3233/JAD-2006-9S347
Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop.
I. McKeith (1996)
10.1002/ANA.410390320
Aβ‐peptide length aid apolipoprotein E genotype in Alzheimer's disease
M. Gearing (1996)
The interaction between apolipoprotein E and Alzheimer's amyloid beta-peptide is dependent on beta-peptide conformation.
A. Golabek (1996)
10.1056/NEJM199603213341202
Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E.
E. Reiman (1996)
10.1016/S0140-6736(05)64588-6
Apolipoprotein-E genotyping in diagnosis of Alzheimer's disease
B. Kakulas (1996)
10.1006/exnr.1996.0064
Differential Binding of Apolipoprotein E Isoforms to Tau and Other Cytoskeletal Proteins
L. Fleming (1996)
10.1074/JBC.271.18.10602
The Interaction between Apolipoprotein E and Alzheimers Amyloid -Peptide Is Dependent on -Peptide Conformation (*)
A. Golabek (1996)
10.1016/S0140-6736(96)01251-2
Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease
A. Saunders (1996)
10.1021/BI952852V
Native complex formation between apolipoprotein E isoforms and the Alzheimer's disease peptide A beta.
W. Chan (1996)
Specificity, sensitivity and predictive value of apolipoprotein E genotyping in a consecutive autopsy series of sporadic Alzheimer disease
AM Saunders (1996)
A beta-peptide length and apolipoprotein E genotype in Alzheimer’s disease
M Gearing (1996)
Apoliprotein E genotypes in a neuropathological series from the Consortium to Establish a Registry for Alzheimer's disease (CER- AD)
Ka Welsh-Bohmer (1996)
10.1001/JAMA.278.16.1349
Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.
L. Farrer (1997)
Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease
L. Farrer (1997)
10.1042/BJ3250169
Apolipoprotein E forms stable complexes with recombinant Alzheimer's disease beta-amyloid precursor protein.
C. Haas (1997)
Further characterization of a monoclonal antibody recognizing apolipoprotein E peptides in amyloid deposits.
T. Yamada (1997)
Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition.
K. Bales (1997)
10.1001/JAMA.1997.03550020068040
Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing.
B. Jordan (1997)
10.1016/S0006-8993(96)01448-5
Severe learning deficits in apolipoprotein E-knockout mice in a water maze task
M. Oitzl (1997)
10.1016/S0006-8993(96)01420-5
Neurodegeneration and cognitive impairment in apoE-deficient mice is ameliorated by infusion of recombinant apoE
E. Masliah (1997)
10.1016/S0006-8993(97)00640-9
Amino-terminus truncated apolipoprotein E is the major species in amyloid deposits in Alzheimer's disease-affected brains: a possible role for apolipoprotein E in Alzheimer's disease
Y. Aizawa (1997)
10.1002/ANA.410420308
Apolipoprotein E genotypes in a neuropathological series from the consortium to establish a registry for Alzheimer's disease
K. Welsh-Bohmer (1997)
10.1016/S0006-8993(97)01533-3
Apolipoprotein-E deficiency results in an altered stress responsiveness in addition to an impaired spatial memory in young mice
Y. Zhou (1998)
10.1002/(SICI)1096-8628(19980207)81:1<117::AID-AJMG19>3.0.CO;2-M
ApoE genotype is a risk factor in nonpresenilin early-onset Alzheimer's disease families.
H. Houlden (1998)
Apolipoprotein E genotype and deposits of Abeta40 and Abeta42 in Alzheimer disease.
M. McNamara (1998)
10.1001/ARCHNEUR.55.7.1001
Apolipoprotein E Genotype and Deposits of Aβ40 and Aβ42 in Alzheimer Disease
M. McNamara (1998)
10.3109/07853899809002605
Molecular genetics of Alzheimer's disease.
M. Cruts (1998)
10.1016/S0002-9440(10)65721-5
Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau.
M. Spillantini (1998)
10.1016/S0306-4522(97)00598-8
Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse
R. Anderson (1998)
10.1016/S0304-3940(98)00180-3
Human apolipoprotein E accelerates microtubule polymerization in vitro
B. Scott (1998)
10.1002/(SICI)1097-4547(19980301)51:5<658::AID-JNR13>3.0.CO;2-Z
Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different signaling pathways
X. Wang (1998)
10.1002/ANA.410430124
Amyloid angiopathy in a volga german family with Alzheimer's disease and a presenilin‐2 mutation (N141I)
D. Nochlin (1998)
10.1046/j.1471-4159.1998.70052070.x
Nascent Astrocyte Particles Differ from Lipoproteins in CSF
M. LaDu (1998)
Accelerated decline in apolipoprotein E-epsilon4 homozygotes with Alzheimer's disease.
S. Craft (1998)
10.1212/WNL.51.1.149
Accelerated decline in apolipoprotein E-ϵ4 homozygotes with Alzheimer's disease
S. Craft (1998)
10.1056/NEJM199802193380804
Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease.
R. Mayeux (1998)
10.1016/S0002-9440(10)65305-9
Specific regional transcription of apolipoprotein E in human brain neurons.
P. Xu (1999)
10.1016/S0896-6273(00)80861-2
Direct Binding of Reelin to VLDL Receptor and ApoE Receptor 2 Induces Tyrosine Phosphorylation of Disabled-1 and Modulates Tau Phosphorylation
T. Hiesberger (1999)
10.1016/S0896-6273(00)80860-0
Reelin Is a Ligand for Lipoprotein Receptors
G. D’Arcangelo (1999)
10.1172/JCI6179
Expression of human apolipoprotein E reduces amyloid-beta deposition in a mouse model of Alzheimer's disease.
D. Holtzman (1999)
10.1097/00041433-199906000-00003
Apolipoprotein E: from atherosclerosis to Alzheimer's disease and beyond.
R. Mahley (1999)
10.1007/s004010051066
Neuronal cytoskeletal changes are an early consequence of repetitive head injury
J. F. Geddes (1999)
J Neuropathol Exp Neurol
Genetic And (2000)
J Neuropathol Exp Neurol
(2000)



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10.3389/fnins.2021.630502
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M. Husain (2021)
10.1007/s11064-021-03315-z
Study on Mechanism of Ginkgo biloba L. Leaves for the Treatment of Neurodegenerative Diseases Based on Network Pharmacology
Jing Wang (2021)
10.1186/s13195-021-00857-w
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Jaeho Kim (2021)
10.3390/s21062067
Plasmonic Nanoparticles as Optical Sensing Probes for the Detection of Alzheimer’s Disease
M. Oyarzún (2021)
10.1111/ejn.15215
Role of triggering receptor expressed on myeloid cells 2 (TREM2) in neurodegenerative dementias
Sadat Shafi (2021)
10.1007/s11064-021-03415-w
Multifaceted Alzheimer's Disease: Building a Roadmap for Advancement of Novel Therapies.
D. Kaur (2021)
10.1101/2020.03.26.010330
Cell type-specific histone acetylation profiling of Alzheimer’s Disease subjects and integration with genetics
Easwaran Ramamurthy (2020)
10.1016/j.nbd.2020.104795
Apolipoprotein E and oxidative stress in brain with relevance to Alzheimer's disease
D. Butterfield (2020)
10.3390/ijms21072381
The Genetics of Alzheimer’s Disease in the Chinese Population
Chen-Ling Gan (2020)
10.1038/s41598-020-72616-0
Presence of the apolipoprotein E-ε4 allele is associated with an increased risk of sepsis progression
Y. Shao (2020)
10.1016/j.neurobiolaging.2020.06.001
Impact of APOE-ε4 carriage on the onset and rates of neocortical Aβ-amyloid deposition
S. Burnham (2020)
10.31083/j.jin.2020.02.110
Genetic factors related to the immune system in subjects at risk of developing Alzheimer's disease.
Michał Prendecki (2020)
10.3233/JAD-180939
Deep White Matter Lesions Are Associated with Early Recognition of Dementia in Alzheimer's Disease.
H. Kasahara (2019)
10.1007/978-981-32-9721-0_3
Genetic Markers of Alzheimer's Disease.
M. Nikolac Perkovic (2020)
10.1111/febs.14794
Conformational analysis of apolipoprotein E3/E4 heteromerization
K. Tu (2019)
10.1016/j.jocn.2019.05.017
Role of APOE and IL18RAP gene polymorphisms in cervical spondylotic myelopathy in Indian population
S. Diptiranjan (2019)
10.1017/S1041610218002089
Impacts of apolipoprotein E disclosure on healthy Asian older adults: a cohort study
Wei Theng Sng (2019)
10.1016/j.trci.2018.03.004
Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease
T. Voss (2018)
10.1155/2017/7420796
Antidiabetic Drugs in Alzheimer's Disease: Mechanisms of Action and Future Perspectives
G. Femminella (2017)
10.1016/B978-0-12-803592-4.00082-1
4.16 – Aging and Alzheimer's Disease
S. Sindi (2017)
Genetic, Biochemical and Cellular Correlates Associated with Alzheimer’s Disease
P. Jairani (2016)
10.1371/journal.pone.0157514
The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer’s Disease
Luise Christine Löwe (2016)
10.1159/000449373
Cognitive Function, APOE Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland
I. Bojar (2016)
10.2147/CIA.S105769
Genes associated with Alzheimer’s disease: an overview and current status
Mohan Giri (2016)
10.4172/2469-6676.100049
Alzheimer's Disease: Pathophysiology, Hypotheses and Treatment Strategies
Azza A. Ali (2016)
10.5772/60024
Neuroinflammation and Alteration of the Blood-Brain Barrier in Alzheimer´s Disease
Luis O Soto-Rojas (2015)
10.1161/STROKEAHA.115.010449
Influence of Amyloid-&bgr; on Cognitive Decline After Stroke/Transient Ischemic Attack: Three-Year Longitudinal Study
Wenyan Liu (2015)
10.3233/JAD-150089
Olfactory Dysfunction in ApoE ɛ4/4 Homozygotes with Alzheimer's Disease.
S. Oleson (2015)
10.1186/s12868-015-0211-1
Neuronal response in Alzheimer’s and Parkinson’s disease: the effect of toxic proteins on intracellular pathways
S. Majd (2015)
10.1016/j.npep.2015.06.008
Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease
Sagar H. Barage (2015)
Predicative genetic testing for Alzheimer's disease.
Tih-Shih Lee (2014)
Different Adenosine A 2 A Receptor Expression in Peripheral Cells from Elderly Patients with Vascular Dementia and Alzheimer ’ s Disease
Cristina Gussagoa (2014)
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