title: Longitudinal cerebrospinal fluid biomarkers over four years in mild cognitive impairment.
abstract: Cerebrospinal fluid (CSF) measurements of amyloid-β42 (Aβ42), total-tau (T-tau), and phosphorylated tau (P-tau) may be used to predict future Alzheimer's disease (AD) dementia in patients with mild cognitive impairment (MCI). The precise temporal development of these biomarkers in relation to clinical progression is unclear. Earlier studies have been hampered by short follow-up. In an MCI cohort, we selected 15 patients who developed AD (MCI-AD) and 15 who remained cognitively stable during 4 years of follow-up. CSF was sampled at three serial occasions from each patient and analyzed for Aβ peptides, the soluble amyloid-β protein precursor protein fragments sAβPPα and sAβPPβ, T-tau, P-tau, and chromogranin B, which is a protein linked to regulated neuronal secretion. We also measured, for the first time in MCI patients, an extended panel of Aβ peptides by matrix-assisted-laser-desorption/ionization time-of-flight mass spectrometry (MS). Most biomarkers were surprisingly stable over the four years with coefficients of variation below or close to 10%. However, MCI-AD patients decreased in CSF AβX₋₄₀ and chromogranin B concentrations, which may indicate a reduced number of functional neurons or synapses with disease progression. The MS Aβ peptide panel was more useful than any single Aβ peptide to identify MCI-AD patients already at baseline. Knowledge on these biomarkers and their trajectories may facilitate early diagnosis of AD and be useful in future clinical trials to track effects of disease modifying drugs.
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. niklas.mattsson@neuro.gu.se
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.forename: Sindre
authors.initials: S
authors.lastname: Rolstad
authors.forename: Mikael
authors.initials: M
authors.lastname: Gustavsson
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.forename: Mats
authors.initials: M
authors.lastname: Stridsberg
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D053379:Chromogranin A / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D053379:Chromogranin A; D016875:tau Proteins