title: Longitudinal stability evaluation of biomarkers and their correlation in cerebrospinal fluid and plasma from patients with Alzheimer's disease.
abstract: There is an increasing demand for biomarkers in clinical treatment trials to demonstrate target engagement and to support disease modification claims. To be able to detect treatment related effects, a prerequisite is that the levels of the biomarker are stable over time or that the change over time is known. In the present study, the stability of α- and β-cleaved soluble amyloid-β protein precursor (sAβPPα and sAβPPβ), Aβ1-40 together with the phosphorylated form of neurofilament heavy/medium (pNfH/M) in cerebrospinal fluid (CSF) was analyzed in a cohort of 51 patients with Alzheimer's disease. In addition, the stability of Aβ1-40, Aβ1-42, and sAβPPβ in plasma was explored. Plasma and CSF was sampled at baseline and after 6-months follow up, and all patients were on stable treatment with acetylcholinesterase inhibitors. During this 6-month longitudinal follow-up, we saw a small, but consistent and statistically significant increase in CSF levels of sAβPPβ (103% of baseline levels) and a statistically significant decrease in the CSF levels of pNfH/M (91% of baseline levels). The mean level of the CSF biomarkers were very stable between baseline and endpoint, with within-patients coefficients of variation (CVs) of 5.84-17.3%, while the variability was larger for the plasma biomarkers, with CVs of 14.1-42.3%. This stability suggests that these biomarkers may have the potential to detect and monitor biochemical changes induced by disease-modifying drugs.
authors.affiliation: AstraZeneca Translational Sciences Centre, Science for Life Laboratory, Solna, Sweden. kina.hoglund@astrazeneca.com
authors.forename: Kina
authors.initials: K
authors.lastname: Höglund
authors.forename: Anna
authors.initials: A
authors.lastname: Bogstedt
authors.forename: Susanne
authors.initials: S
authors.lastname: Fabre
authors.forename: Ali
authors.initials: A
authors.lastname: Aziz
authors.forename: Peter
authors.initials: P
authors.lastname: Annas
authors.forename: Hans
authors.initials: H
authors.lastname: Basun
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid; D055550:Protein Stability
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C051774:neurofilament protein H