CSF BIOMARKERS OF NEUROINFLAMMATION ARE ELEVATED IN PRECLINICAL AND PRODROMAL AD AND CORRELATE WITH TAU PATHOLOGY

Abstract

Neuroinflammation has been implicated in the pathophysiology of Alzheimer's disease (AD). Here we investigated if neuroinflammatory changes occur in the early stages of the disease, e.g. preclinical and prodromal AD. The study population included a cohort of 875 individuals (the Swedish BioFINDER study), including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD and cognitively healthy elderly. Cerebrospinal fluid (CSF) concentrations of a panel of inflammatory biomarkers were measured using ultrasensitive MSD immunoassay. We also analyzed CSF levels Aβ42, Aβ40 and p-tau. Study participants were categorized into groups with normal (N) or pathological (P) Aβ status using the CSF Aβ42/Aβ40 ratio cutoff<0.1. Inflammatory biomarkers, YKL-40, ICAM-1, VCAM-1 and IL-15 were already increased in preclinical AD stage (control-P group) and remained elevated in prodromal (SCD-P, MCI-P) and dementia stages of AD compared to control-N groups. IL-8 was higher in SCD-P, MCI-P and AD but not in control-P group. The inflammatory biomarkers correlated with CSF p-tau. Furthermore, correlations between p-tau and YKL-40, ICAM-1, VCAM-1 and IL-15 were stronger in CSF Aβ-positive than in Aβ-negative individuals. In this large clinical study we demonstrate that in AD, neuroinflammatory responses are activated early in the disease course, long before the onset of clinical symptoms. Our data also indicate that neuroinflammation may partially trigger AD-related tau pathology especially in cases with amyloid pathology.