التفاصيل البيبلوغرافية
| العنوان: |
CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders |
| المؤلفون: |
Mattsson, Niklas, 1979, Insel, P., Nosheny, R., Zetterberg, Henrik, 1973, Trojanowski, J. Q., Shaw, L. M., Tosun, D., Weiner, M. |
| المصدر: |
Translational Psychiatry. 3 |
| مصطلحات موضوعية: |
Neurosciences, Neurovetenskaper, Alzheimer's disease, Beta-amyloid, Biomarker, Cerebrospinal fluid, Longitudinal, Microglia, amyloid beta protein[1-42], beta 2 microglobulin, CD40 antigen, chromogranin A, clusterin, colony stimulating factor 1, CXCL9 chemokine, dipeptidyl carboxypeptidase, fibrinogen, follitropin, immunoglobulin A, monocyte chemotactic protein 1, osteopontin, plasminogen activator inhibitor 1, protein tyrosine kinase, serum amyloid P, somatomedin binding protein 2, tau protein, tissue inhibitor of metalloproteinase, tumor necrosis factor receptor 2, tumor necrosis factor related apoptosis inducing ligand, von Willebrand factor, aged, Alzheimer disease, amyloid plaque, article, cerebrospinal fluid analysis, controlled study, female, follow up, human, longitudinal study, male, Mini Mental State Examination, normal human, protein cerebrospinal fluid level, protein metabolism, synapse, synaptic potential |
| الوصف: |
β-amyloid (Ab) plaque accumulation is a hallmark of Alzheimer's disease (AD). It is believed to start many years prior to symptoms and is reflected by reduced cerebrospinal fluid (CSF) levels of the peptide Aβ1-42 (Aβ42). Here we tested the hypothesis that baseline levels of CSF proteins involved in microglia activity, synaptic function and Ab metabolism predict the development of Ab plaques, assessed by longitudinal CSF Aβ42 decrease in cognitively healthy people. Forty-six healthy people with three to four serial CSF samples were included (mean follow-up 3 years, range 2-4 years). There was an overall reduction in Aβ42 from a mean concentration of 211-195 pg ml1 after 4 years. Linear mixed-effects models using longitudinal Aβ42 as the response variable, and baseline proteins as explanatory variables (n=69 proteins potentially relevant for Ab metabolism, microglia or synaptic/neuronal function), identified 10 proteins with significant effects on longitudinal Aβ42. The most significant proteins were angiotensinconverting enzyme (ACE, P=0.009), Chromogranin A (CgA, P=0.009) and Axl receptor tyrosine kinase (AXL, P=0.009). Receiveroperating characteristic analysis identified 11 proteins with significant effects on longitudinal Aβ42 (largely overlapping with the proteins identified by linear mixed-effects models). Several proteins (including ACE, CgA and AXL) were associated with Aβ42 reduction only in subjects with normal baseline Aβ42, and not in subjects with reduced baseline Aβ42. We conclude that baseline CSF proteins related to Ab metabolism, microglia activity or synapses predict longitudinal Aβ42 reduction in cognitively healthy elders. The finding that some proteins only predict Aβ42 reduction in subjects with normal baseline Aβ42 suggest that they predict future development of the brain Ab pathology at the earliest stages of AD, prior to widespread development of Aβ plaques. © 2013 Macmillan Publishers Limited All rights reserved. |
| الوصول الحر: |
https://gup.ub.gu.se/publication/195804Test |
| قاعدة البيانات: |
SwePub |
