Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease

Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases

Reflecting on populism and the economics of globalization

First Online: 06 April 2018In this commentary, we take up two key elements of Dani Rodrik’s analysis of the economic underpinnings of populist politics. We focus on the links between globalization (especially trade integration) and populism and the role of global institutions (notably trade agreements) in both generating the economic pressures to which populist politicians are responding and in constraining the ability of governments to deal with adverse distributional effects of these pressures. We argue that it is important to distinguish between trade shocks and trade agreements; that the role of both is given too much weight relative to the effects of financialization and international capital flows, migration, and technological change; and that deepening international cooperation (global governance) can – and should – be part of the supply response to populism