Association of CSF Proteins With Tau and Amyloid β Levels in Asymptomatic 70-year-olds

BackgroundIncreased 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 recognised, the need for further characterization of the pathophysiological mechanisms behind AD still remains.MethodsIn 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-based technology. ResultsThe protein levels were first correlated with the core AD CSF biomarker concentrations of total tau, phospho-tau and Aβ42 in all individuals. Sixty-three proteins showed significant correlations with 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 to 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.ConclusionsWe identified a series of transmembrane proteins, proteins associated to or anchored to the plasma membrane, and proteins involved in or connected to synaptic vesicle transport that were associated with CSF biomarkers of amyloid and tau pathology in AD. Further studies are needed to explore their role in AD pathophysiology.