A oligomers peak in early stages of Alzheimer's disease preceding tau pathology

INTRODUCTION: Soluble amyloid beta (A beta) oligomers have been suggested as initiating A beta related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear. METHODSA total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. A beta and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface-based fluorescence intensity distribution analysis (sFIDA) technology. RESULTS: Across groups, highest A beta oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. A beta oligomers were significantly higher in A+T- compared to A-T- and A+T+. APOE epsilon 4 allele carriers showed significantly higher A beta oligomer levels. No differences in tau oligomers were detected. DISCUSSIONThe accumulation of A beta oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease-modifying treatments targeting A beta oligomers might have the highest therapeutic effect in these disease stages.