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Longitudinal cerebrospinal fluid biomarkers over four years in mild cognitive impairment.

Journal article
Authors Niklas Mattsson
Erik Portelius
Sindre Rolstad
Mikael K Gustavsson
Ulf Andreasson
Mats Stridsberg
Anders Wallin
Kaj Blennow
Henrik Zetterberg
Published in Journal of Alzheimer's disease : JAD
Volume 30
Issue 4
Pages 767-78
ISSN 1875-8908
Publication year 2012
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 767-78
Language en
Keywords Aged, Alzheimer Disease, cerebrospinal fluid, diagnosis, Amyloid beta-Peptides, cerebrospinal fluid, Biological Markers, cerebrospinal fluid, Chromogranin A, cerebrospinal fluid, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Mild Cognitive Impairment, cerebrospinal fluid, diagnosis, tau Proteins, cerebrospinal fluid
Subject categories Neurology


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.

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