The effect of apolipoprotein E (ApoE) genotype on biomarkers of amyloidogenesis, tau pathology and neurodegeneration in Alzheimer's disease
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Valerio Leoni
Abstract
The presence of the ɛ4 allele in apolipoprotein E (ApoE) represents the most important genetic risk factor for late onset sporadic Alzheimer's disease (AD), together with age and mid-life hypercholesterolemia. ApoE4 is the most important lipid transporter between cells in the CNS and it was found that ApoE4 is involved in Amyloid β (Aβ) formation, fibrilisation, accumulation, in the aggregation and hyperphosphorylation of tau and in the metabolism of brain cholesterol and in neurodegeneration. Low cerebrospinal fluid (CSF) Aβ1-42 is a marker of Aβ plaque load in the brain. High CSF t-tau and p-tau concentrations reflect axonal and neuronal damage and injury, which correlates with a neurofibrillary tangle stage and load, also reflecting the intensity of the disease process. Magnetic resonance imaging (MRI) brain atrophy is a biomarker of neurodegeneration and is the result of loss of neurons, synapses and dendritic arborization. ApoE genotype interacts with the AD biomarkers: ɛ4 carriers were found to present with lower concentrations of Aβ1-42, higher tau and p-tau, higher tau/Aβ ratio and a higher degree of brain atrophy at any disease stage, changing the test performances and the ability to distinguish between the different cognitive condition. The presence of the ɛ4 allele was also found to increase the power to predict further cognitive decline. Even if the presence of ApoE4 is not a deterministic factor for AD, it seems to shift the progression of the disease towards a younger age and faster progression. It is also likely that the ɛ4 allele increases the intensity of the pathological process in several ways. In the study of cognitive impaired patients and in their follow-up, biomarkers should be interpreted in consideration of the ApoE genotype in order to better predict the progression of the disease.
©2011 by Walter de Gruyter Berlin New York
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- Editorial
- Biomarkers of neurodegenerative diseases
- Reviews
- CSF biomarkers in neurodegenerative diseases
- Tau and p-tau as CSF biomarkers in dementia: a meta-analysis
- Amyloid β (Aβ) and phospho-tau (p-tau) as diagnostic biomarkers in Alzheimer's disease
- The effect of apolipoprotein E (ApoE) genotype on biomarkers of amyloidogenesis, tau pathology and neurodegeneration in Alzheimer's disease
- Advanced glycation endproducts as gerontotoxins and biomarkers for carbonyl-based degenerative processes in Alzheimer's disease
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- S100B protein in neurodegenerative disorders
- Inflammatory and structural biomarkers in acute traumatic spinal cord injury
- Homocysteine: a biomarker in neurodegenerative diseases
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- Erythrocyte membrane protein analysis by sodium dodecyl sulphate-capillary gel electrophoresis in the diagnosis of hereditary spherocytosis
- Evaluation of hematological parameters on admission for the prediction of 7-day in-hospital mortality in a large trauma cohort
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- Letters to the Editor
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Articles in the same Issue
- Editorial
- Biomarkers of neurodegenerative diseases
- Reviews
- CSF biomarkers in neurodegenerative diseases
- Tau and p-tau as CSF biomarkers in dementia: a meta-analysis
- Amyloid β (Aβ) and phospho-tau (p-tau) as diagnostic biomarkers in Alzheimer's disease
- The effect of apolipoprotein E (ApoE) genotype on biomarkers of amyloidogenesis, tau pathology and neurodegeneration in Alzheimer's disease
- Advanced glycation endproducts as gerontotoxins and biomarkers for carbonyl-based degenerative processes in Alzheimer's disease
- Parkinson's disease – the continuing search for biomarkers
- α-Synuclein in Parkinson disease and other neurodegenerative disorders
- S100B protein in neurodegenerative disorders
- Inflammatory and structural biomarkers in acute traumatic spinal cord injury
- Homocysteine: a biomarker in neurodegenerative diseases
- Editorial
- ROMA or death: advances in epithelial ovarian cancer diagnosis
- Review
- Laboratory testing for the antiphospholipid syndrome: making sense of antiphospholipid antibody assays
- General Clinical Chemistry and Laboratory Medicine
- Quality indicators and specifications for key analytical-extranalytical processes in the clinical laboratory. Five years’ experience using the Six Sigma concept
- Determination of oxidative and occupational stress in palliative care workers
- Effect of cigarette smoking on plasma homocysteine concentrations
- Erythrocyte membrane protein analysis by sodium dodecyl sulphate-capillary gel electrophoresis in the diagnosis of hereditary spherocytosis
- Evaluation of hematological parameters on admission for the prediction of 7-day in-hospital mortality in a large trauma cohort
- Platelet function testing in hirudin and BAPA anticoagulated blood
- Evaluation of the iChem® Velocity™ Urine Chemistry Analyzer in a hospital routine laboratory
- Crystalluria: prevalence, different types of crystals and the role of infrared spectroscopy
- Cancer Diagnostics
- The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful?
- Evaluation of the accuracy of serum human epididymis protein 4 in combination with CA125 for detecting ovarian cancer: a prospective case-control study in a Korean population
- Cardiovascular Diseases
- APOA5 −1131T/C polymorphism is associated with coronary artery disease in a Chinese population: a meta-analysis
- Assessment of the nickel-albumin binding assay for diagnosis of acute coronary syndrome
- Letters to the Editor
- AGER gene -374T>A (rs1800624) polymorphism is not associated with the severity of non-diabetic coronary artery disease in Han Chinese
- Some lessons learned from using medium scale genotyping techniques in pharmacogenetic research
- Improved neopterin ELISA kit: a good compromise between HPLC results and clinical practice
- Cross-reactivity of 25-hydroxy vitamin D2 from different commercial immunoassays for 25-hydroxy vitamin D: an evaluation without spiked samples
- Modulated human maternal and premature neonatal erythrocyte membrane enzyme activities in relation to the mode of delivery: in vitro restoration with L-Carnitine
