PMC:6194691 / 160954-162547 JSONTXT

{"project":"MyTest","denotations":[{"id":"30340614-21148344-30706533","span":{"begin":1135,"end":1138},"obj":"21148344"},{"id":"30340614-20838242-30706534","span":{"begin":1241,"end":1244},"obj":"20838242"},{"id":"30340614-20010299-30706535","span":{"begin":1246,"end":1249},"obj":"20010299"},{"id":"30340614-25204284-30706536","span":{"begin":1433,"end":1436},"obj":"25204284"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Estimating the value of the total clearance of soluble Aβ from ISF\nCalculating a clearance value for the elimination of Aβ from ISF is not straightforward as much of the Aβ in ISF is complexed with other solutes, e.g. apoE and clusterin. However, an estimate can be made if it is assumed that all the forms that are accessible to be eliminated are dissolved in the ISF and eliminated with the same rate constant. The volume of distribution for the total soluble Aβ, whether or not as part of complexes, will be that of ISF and thus the clearance can be calculated as rate constant × volume of distribution = 0.05 min−1 × 0.2 mL g−1 = 10 µL g−1 min−1. On this basis perivascular clearance, expected using the same assumptions to be about 1 µL g−1 min−1, may be about 1/10th as large, a small but still significant fraction of the total.\nIn all of the preceding, the rates of elimination by various routes have been considered almost as if they are constant. However, reduction in the overall clearance and thus in the rates of elimination by some of the routes are likely to be very important in the development of Alzheimer’s disease [422]. In this regard LRP1 expression has been found to be reduced and RAGE expression increased with age [478, 513]. Similarly perivascular elimination has been found to decrease with age possibly as a result of decreased variations in the size of arteries and arterioles during the cardiac cycle [514] (see Sect. 3.2). All of these changes will tend to increase Aβ ISF concentration and hence lead to increased formation of plaques and vascular Aβ deposits."}

{"project":"2_test","denotations":[{"id":"30340614-21148344-30706533","span":{"begin":1135,"end":1138},"obj":"21148344"},{"id":"30340614-20838242-30706534","span":{"begin":1241,"end":1244},"obj":"20838242"},{"id":"30340614-20010299-30706535","span":{"begin":1246,"end":1249},"obj":"20010299"},{"id":"30340614-25204284-30706536","span":{"begin":1433,"end":1436},"obj":"25204284"}],"text":"Estimating the value of the total clearance of soluble Aβ from ISF\nCalculating a clearance value for the elimination of Aβ from ISF is not straightforward as much of the Aβ in ISF is complexed with other solutes, e.g. apoE and clusterin. However, an estimate can be made if it is assumed that all the forms that are accessible to be eliminated are dissolved in the ISF and eliminated with the same rate constant. The volume of distribution for the total soluble Aβ, whether or not as part of complexes, will be that of ISF and thus the clearance can be calculated as rate constant × volume of distribution = 0.05 min−1 × 0.2 mL g−1 = 10 µL g−1 min−1. On this basis perivascular clearance, expected using the same assumptions to be about 1 µL g−1 min−1, may be about 1/10th as large, a small but still significant fraction of the total.\nIn all of the preceding, the rates of elimination by various routes have been considered almost as if they are constant. However, reduction in the overall clearance and thus in the rates of elimination by some of the routes are likely to be very important in the development of Alzheimer’s disease [422]. In this regard LRP1 expression has been found to be reduced and RAGE expression increased with age [478, 513]. Similarly perivascular elimination has been found to decrease with age possibly as a result of decreased variations in the size of arteries and arterioles during the cardiac cycle [514] (see Sect. 3.2). All of these changes will tend to increase Aβ ISF concentration and hence lead to increased formation of plaques and vascular Aβ deposits."}