Can Syndecan-1 Be Used As A Biomarker In Alzheimer’s Disease? (original) (raw)
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Chondroitin Sulfate Proteoglycans Are Associated with the Lesions of Alzheimer's Disease
Experimental Neurology, 1993
Chondroitin sulfate proteoglycans (CSPG) are extracellular matrix proteins inhibitory to neurite outgrowth in vitro and correlated with decreased neurite outgrowth after CNS injury. Previously, heparan sulfate proteoglycan and dermatan sulfate proteoglycan have been shown to be associated with senile plaques (SPs) and neurofibrillary tangles (NFTs) but CSPG was not. In an immunocytochemical study, three monoclonal antibodies to different sulfation states of the chondroitin glycosaminoglycan were used to localize CSPG in cases of Alzheimer's disease. Chondroitin 4-sulfate was found in both SPs and NFTs. An antibody to unsulfated chondroitin strongly immunostained intracellular NFTs and the dystrophic neurites of SPs. Chondroitin 6-sulfate was found in NFTs and the area around SPs. These results suggest that CSPG, in addition or as an alternative to ~-amyloid protein, could be responsible for the regression of neurites around senile plaques in Alzheimer's disease.
Agrin Is a Major Heparan Sulfate Proteoglycan Accumulating in Alzheimer's Disease Brain
The American Journal of Pathology, 1999
Heparan sulfate proteoglycans (HSPGs) have been suggested to play an important role in the formation and persistence of senile plaques and neurofibrillary tangles in dementia of the Alzheimer's type (DAT). We performed a comparative immunohistochemical analysis of the expression of the HSPGs agrin , perlecan , glypican-1 , and syndecans 1-3 in the lesions of DAT brain neocortex and hippocampus. Using a panel of specific antibodies directed against the protein backbone of the various HSPG species and against the glycosaminoglycan (GAG) side-chains, we demonstrated the following. The basement membrane-associated HSPG , agrin , is widely expressed in senile plaques , neurofibrillary tangles and cerebral blood vessels , whereas the expression of the other basement membrane-associated HSPG , perlecan, is lacking in senile plaques and neurofibrillary tangles and is restricted to the cerebral vasculature. Glypican and three different syndecans , all cell membraneassociated HSPG species , are also expressed in senile plaques and neurofibrillary tangles , albeit at a lower frequency than agrin. Heparan sulfate GAG side chains are also associated with both senile plaques and neurofibrillary tangles. Our results suggest that glycosaminoglycan side chains of the HSPGs agrin, syndecan , and glypican , but not perlecan , may play an important role in the formation of both senile plaques and neurofibrillary tangles. In addition, we speculate that agrin , because it contains nine protease-inhibiting domains , may protect the protein aggregates in senile plaques and neurofibrillary tangles against extracellular proteolytic degradation , leading to the persistence of these deposits. Supported by the Internationale Stichting Alzheimer Onderzoek.
Alzheimer s disease and heparan sulfate proteoglycan
Frontiers in Bioscience, 1998
Introduction 3. Discussion 3.1. Chemistry of heparan sulfate proteoglycan 3.2. Chemical composition of heparan sulfate in Alzheimer's disease 3.3. Immunohistochemical localization of heparan sulfate proteoglycan 3.4. Beta-amyloid protein and its precursor protein 3.5. Beta-amyloidosis and heparan sulfate proteoglycan 3.5.1. Interaction between beta-amyloid protein and heparan sulfate proteoglycan 3.5.2. Rat infusion models of brain amyloidosis 3.5.3. Processing of amyloid precursor protein and heparan sulfate proteoglycan 3.5.4. Beta-amyloid clearance and heparan sulfate proteoglycan 3.6. Neurite outgrowth and heparan sulfate proteoglycan 3.7. Neurofibrillary tangles and heparan sulfate proteoglycan 3.8. Apolipoprotein and heparan sulfate proteoglycan 4. Perspective 5. Acknowledgments 6. References
Biomarkers for Identifying Individuals at Risk of Alzheimer Disease
International Journal of Emergency Mental Health and Human Resilience, 2018
Background: Alzheimer Disease (AD), the most common form of dementia, is a progressive and irreversible neurodegenerative disorder. Promising preventative strategies includes identification of potential modifiable risk factors for AD that could help identify individual who are at risk of AD. This study focuses on identifying biochemical factors associated with non-familial AD. Methods: One hundred and ten individuals which included 55 AD patients and 55 healthy controls were recruited for the study. Patients clinically diagnosed by a neurologist as AD and controls with no clinical or family history of any neurological disease were subjected to Mini-Mental State Examination (MMSE) were evaluated for fourteen relevant biochemical markers using commercial kits. MDR analysis was carried out which is considered a basic machine learning tool for understanding the role of interaction and combination of the factors towards the outcome. PCA is performed to support the MDR interpretation. Through clustering analysis the probably causative factors towards the disease can be identified. Results: MDR analysis revealed that the overall best fit model included 10 factors which had a maximal testing accuracy of 61%, cross-validation consistency of 8/10. PCA analysis has further reduced the factors to Iron, TSAT, HDL, VitB12, FA, and Hcy which are important in disease initiation/progression. Apart from the cases, 9% of the controls who had lower MMSE also had low Iron, TSAT, HDL, VitB12, FA, and high Hcy. Conclusion: As per the results obtained, we would suggest a medical practice where, screening individuals above the age of 55 years with both MMSE and selected biochemical parameters (Iron, TSAT, HDL, VitB12, FA, and Hcy) should be carried out to identify those at risk of developing AD. Higher risk individuals can be suggested for modifications in diet/life style, enhancing certain nutritional components which may constitute promising strategies in postponing, slowing, and/or preventing cognitive decline in AD.
The Role of Heparan Sulfate Proteoglycans in the Pathogenesis of Alzheimer's Diseasea
Annals of the New York Academy of Sciences, 1996
The hallmark of Alzheimer's disease (AD) is the deposition of amyloid plaques and neurofibrillary tangles in the brain. The relationship between amyloid deposition and the cognitive deficit is still unclear. The amyloid PA4 protein is produced by proteolytic cleavage of the amyloid protein precursor (APP). Very little is known about the normal function of APP and the role the protein may play in pathogenesis. Several studies have shown that APP is important for the regulation of neurite outgrowth. Our studies support these findings and indicate that the neurite outgrowth-promoting effects of APP are stimulated
Alzheimer's Disease Biomarkers and Cognition
Alzheimer's & Dementia, 2014
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Biomarkers for cognitive impairment and dementia in elderly people
The Lancet Neurology, 2008
The threat of a looming pandemic of dementia in elderly people highlights the compelling need for the development and validation of biomarkers that can be used to identify pre-clinical and prodromal stages of disease in addition to fully symptomatic dementia. Although predictive risk factors and correlative neuroimaging measures will have important roles in these efforts, this Review describes recent progress in the discovery, validation, and standardization of molecular biomarkers -small molecules and macromolecules whose concentration in brain or biological fluids can aid in diagnosis at different stages of the more common dementing diseases and in the assessment of disease progression and response to therapeutics. An approach that efficiently combines independent information from risk factor assessment, neuroimaging measures, and biomarkers may soon guide clinicians in the early diagnosis and management of cognitive impairment in elderly people.
International Journal of Molecular Sciences
Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn alone. Regression analyses showed an association of higher Ng concentrations with MMSE < 24, pathological Aβ 42/40 ratios, pTau, tTau and the ApoEε4 genotype. Aβ 42/Ng was associated with MMSE < 24, an AD-related FDG-PET pattern, the ApoEε4 genotype, pathological Aβ 42 levels and Aβ 42/40 ratios, pTau, and tTau. Moreover, APO-Eε4 carri...