Cerebrospinal Fluid Profiles of Amyloid beta-Related Biomarkers in Alzheimers Disease
2012 (English)In: Neuromolecular medicine, ISSN 1535-1084, E-ISSN 1559-1174, Vol. 14, no 1, 65-73 p.Article in journal (Refereed) Published
The amyloid cascade hypothesis on the pathogenesis of Alzheimers disease (AD) states that amyloid beta (A beta) accumulation in the brain is a key factor that initiates the neurodegenerative process. A beta is generated from amyloid precursor protein (APP) through sequential cleavages by BACE1 (the major beta-secretase in the brain) and gamma-secretase. The purpose of this study was to characterize APP metabolism in vivo in AD patients versus cognitively healthy subjects by examining alterations in cerebrospinal fluid (CSF) biomarkers. We measured BACE1 activity and concentrations of alpha- and beta-cleaved soluble APP (sAPP alpha and sAPP beta, respectively) and A beta 40 in CSF, biomarkers that all reflect the metabolism of APP, in 75 AD patients and 65 cognitively healthy controls. These analytes were also applied in a multivariate model to determine whether they provided any added diagnostic value to the core CSF AD biomarkers A beta 42, T-tau, and P-tau. We found no significant differences in BACE1 activity or sAPP alpha, sAPP beta, and A beta 40 concentrations between AD patients and controls. A multivariate model created with all analytes did not improve the separation of AD patients from controls compared with using the core AD biomarkers alone, highlighting the strong diagnostic performance of A beta 42, T-tau, and P-tau for AD. However, AD patients in advanced clinical stage, as determined by low MMSE score (a parts per thousand currency sign20), had lower BACE1 activity and sAPP alpha, sAPP beta, and A beta 40 concentrations than patients with higher MMSE score, suggesting that these markers may be related to the severity of the disease.
Place, publisher, year, edition, pages
Humana Press (Springer Imprint) , 2012. Vol. 14, no 1, 65-73 p.
Alzheimer, APP, Biomarkers, Amyloid beta, Cerebrospinal fluid, BACE1
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-76530DOI: 10.1007/s12017-012-8171-4ISI: 000301589200006OAI: oai:DiVA.org:liu-76530DiVA: diva2:515138
Funding Agencies|Swedish Research Council||Soderberg Foundation||Alzheimers Association||Swedish Brain Power||Swedish State Support for Clinical Research||Lundbeck Foundation||Stiftelsen Psykiatriska Forskningsfonden||Stiftelsen Gamla Tjanarinnor||Goteborg Medical Society||Thureus stiftelse||Pfannenstills stiftelse||Demensfonden||Uppsala Universitets Medicinska Fakultets stiftelse for psykiatrisk och neurologisk forskning, Alzheimerfonden||2012-04-122012-04-112012-04-12