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

INTRODUCTION Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear. METHODS A 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. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface-based fluorescence intensity distribution analysis (sFIDA) technology. RESULTS Across groups, highest Aβ oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. Aβ oligomers were significantly higher in A+T− compared to A−T− and A+T+. APOE ε4 allele carriers showed significantly higher Aβ oligomer levels. No differences in tau oligomers were detected. DISCUSSION The accumulation of Aβ oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease-modifying treatments targeting Aβ oligomers might have the highest therapeutic effect in these disease stages. Highlights Using surface-based fluorescence intensity distribution analysis (sFIDA) technology, we quantified Aβ oligomers in cerebrospinal fluid (CSF) samples of the DZNE-Longitudinal Cognitive Impairment and Dementia (DELCODE) cohort Aβ oligomers were significantly elevated in mild cognitive impairment (MCI) Amyloid-positive subjects in the subjective cognitive decline (SCD) group increased compared to the amyloid-negative control group Interestingly, levels of Aβ oligomers decrease at advanced stages of the disease (A+T+), which might be explained by altered clearing mechanism

Shifts in Phytoplankton Community Structure Across an Anticyclonic Eddy Revealed From High Spectral Resolution Lidar Scattering Measurements

WOS:000548189100001International audienceChanges in airborne high spectral resolution lidar (HSRL) measurements of scattering, depolarization, and attenuation coincided with a shift in phytoplankton community composition across an anticyclonic eddy in the North Atlantic. We normalized the total depolarization ratio (delta) by the particulate backscattering coefficient (b(b)(p)) to account for the covariance in delta and b(b)(p) that has been attributed to multiple scattering. A 15% increase in delta/b(b)(p) inside the eddy coincided with decreased phytoplankton biomass and a shift to smaller and more elongated phytoplankton cells. Taxonomic changes (reduced dinoflagellate relative abundance inside the eddy) were also observed. The delta signal is thus potentially most sensitive to changes in phytoplankton shape because neither the observed change in the particle size distribution (PSD) nor refractive index (assuming average refractive indices) are consistent with previous theoretical modeling results. We additionally calculated chlorophyll-a (Chl) concentrations from measurements of the diffuse light attenuation coefficient (K-d) and divided by b(b)(p) to evaluate another optical metric of phytoplankton community composition (Chl:b(bp)), which decreased by more than a factor of two inside the eddy. This case study demonstrates that the HSRL is able to detect changes in phytoplankton community composition. High spectral resolution lidar measurements reveal complex structures in both the vertical and horizontal distribution of phytoplankton in the mixed layer providing a valuable new tool to support other remote sensing techniques for studying mixed layer dynamics. Our results identify fronts at the periphery of mesoscale eddies as locations of abrupt changes in near-surface optical properties