USING EMERGING CEREBROSPINAL FLUID MARKERS TO CHARACTERIZE SUSPECTED NON-ALZHEIMER’S DISEASE PATHOPHYSIOLOGY (SNAP) IN INDIVIDUALS WITH MILD COGNITIVE IMPAIRMENT

Abstract

The underlying pathophysiology of individuals with suspected non-Alzheimer's disease pathophysiology (SNAP; biomarker profile with neuronal injury without amyloid pathology) is to date still unclear. Our aim was to investigate the role of inflammation and lipid transport in individuals with mild cognitive impairment (MCI) and SNAP using emerging markers in cerebrospinal fluid (CSF). We selected 77 subjects with MCI and 15 cognitively normal (CN) subjects from the European EDAR study. We measured C3a (central to the classical, alternative and lectin complement pathways), the soluble C5b-9 terminal complement complex (TCC), amyloid binding proteins heart-fatty acid binding protein (HFABP), amyloid beta(Aβ)1–42, total tau (t-tau), and phosphorylated tau (p-tau) in CSF, and serum amyloid P (SAP, an acute response protein which activates complement). CN subjects had normal Aβ1–42 and tau. MCI subjects were classified as having low AD likelihood (n=18, normal Aβ1–42 and tau), SNAP (n=14, normal Aβ1–42 and abnormal tau), isolated amyloid pathology (IAP n=18; abnormal Aβ1–42 and normal tau), or high AD likelihood (n=27, abnormal Aβ1–42 and tau). We compared MCI subgroups using ANOVA and correlated emerging and core CSF Alzheimer's disease markers using Spearman (rho). CN individuals had higher levels of C3a than all MCI groups. Individuals with MCI-SNAP and MCI-high AD likelihood had higher levels of HFABP compared to those with MCI-low AD likelihood and MCI-IAP. Individuals with MCI-high AD likelihood had also higher levels of HFABP than CN individuals (see Table 1). In individuals with MCI, C3a correlated with p-tau (r=0.311, p=0.025), and HFABP correlated with Aβ1–42 (r=-0.242, p=0.034), t-tau (r=0.641, p<0.001) and p-tau (r=0.489, p<0.001). Our findings suggest that inflammation plays a similar role in neurodegeneration within all MCI subgroups. Moreover, HFABP levels are related to overall tau-related neurodegeneration in individuals with MCI.