Journal Article

Association of CSF proteins with tau and amyloid β levels in asymptomatic 70-year-olds

Remnestål, Julia, Månberg, Anna, Bergström, Sofia, Sjöstedt, Evelina, Kern, Silke, Uhlén, Mathias, Zettergren, Anna, Nilsson, Peter, Blennow, Kaj, Zetterberg, Henrik, Olofsson, Jennie, Skoog, Ingmar

2021

Overview

Background Increased knowledge of the evolution of molecular changes in neurodegenerative disorders such as Alzheimer’s disease (AD) is important for the understanding of disease pathophysiology and also crucial to be able to identify and validate disease biomarkers. While several biological changes that occur early in the disease development have already been recognized, the need for further characterization of the pathophysiological mechanisms behind AD still remains. Methods In this study, we investigated cerebrospinal fluid (CSF) levels of 104 proteins in 307 asymptomatic 70-year-olds from the H70 Gothenburg Birth Cohort Studies using a multiplexed antibody- and bead-based technology. Results The protein levels were first correlated with the core AD CSF biomarker concentrations of total tau, phospho-tau and amyloid beta (Aβ42) in all individuals. Sixty-three proteins showed significant correlations to either total tau, phospho-tau or Aβ42. Thereafter, individuals were divided based on CSF Aβ42/Aβ40 ratio and Clinical Dementia Rating (CDR) score to determine if early changes in pathology and cognition had an effect on the correlations. We compared the associations of the analysed proteins with CSF markers between groups and found 33 proteins displaying significantly different associations for amyloid-positive individuals and amyloid-negative individuals, as defined by the CSF Aβ42/Aβ40 ratio. No differences in the associations could be seen for individuals divided by CDR score. Conclusions We identified a series of transmembrane proteins, proteins associated with or anchored to the plasma membrane, and proteins involved in or connected to synaptic vesicle transport to be associated with CSF biomarkers of amyloid and tau pathology in AD. Further studies are needed to explore these proteins’ role in AD pathophysiology.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: AD pathophysiology / Affinity proteomics / Alzheimer Disease / Alzheimer's disease / Amyloid beta-Peptides / Antibodies / Asymptomatic / Biomarkers / Biomedical and Life Sciences / Biomedicine / Brain-enriched proteins / Cerebrospinal fluid / Cerebrospinal Fluid Proteins / CSF markers / Dementia / Enzymes / Epidemiology / Geriatric Psychiatry / Geriatrics/Gerontology / Humans / Multidisciplinary epidemiological studies / Neurodegeneration / Neurology / Neurosciences / Neurovetenskaper / Older people / Pathology / Peptide Fragments / Preclinical Alzheimer’ / Preclinical Alzheimer’s disease / Proteins / s disease / tau Proteins