Proteomic changes in Alzheimer's disease associated with progressive Aβ plaque and tau tangle pathologies.

Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer's disease (AD). Combining radioligands measuring β-amyloid (Aβ) plaques and tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology in living humans. We found 127 differentially abundant proteins (DAPs) across the AD spectrum.

Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling.

The pathophysiology underlying various manifestations of cerebral small vessel disease (cSVD) remains obscure. Using cerebrospinal fluid proximity extension assays and co-expression network analysis of 2,943 proteins, we found common and distinct proteomic signatures between white matter lesions (WML), microbleeds and infarcts measured in 856 living patients, and validated WML-associated proteins in three additional datasets. Proteins indicative of extracellular matrix dysregulation and vascular remodeling, including ELN, POSTN, CCN2 and MMP12 were elevated across all cSVD manifestations, with MMP12 emerging as an early cSVD indicator.

The impact of tau deposition and hypometabolism on cognitive impairment and longitudinal cognitive decline.

Introduction: Tau and neurodegeneration strongly correlate with cognitive impairment, as compared to amyloid. However, their contribution in explaining cognition and predicting cognitive decline in memory clinics remains unclarified.

Methods: We included 94 participants with Mini-Mental State Examination (MMSE), tau positron emission tomography (PET), amyloid PET, fluorodeoxyglucose (FDG) PET, and MRI scans from Geneva Memory Center.

Use of metal-based contrast agents for in vivo MR and CT imaging of phagocytic cells in neurological pathologies.

The activation of phagocytic cells is a hallmark of many neurological diseases. Imaging them in their 3-dimensional cerebral environment over time is crucial to better understand their role in disease pathogenesis and to monitor their potential therapeutic effects. Phagocytic cells have the ability to internalize metal-based contrast agents both in vitro and in vivo and can thus be tracked by magnetic resonance imaging (MRI) or computed tomography (CT).

Sleep decreases neuronal activity control of microglial dynamics in mice.

Microglia, the brain-resident immune cells, are highly ramified with dynamic processes transiently contacting synapses. These contacts have been reported to be activity-dependent, but this has not been thoroughly studied yet, especially in physiological conditions. Here we investigate neuron-microglia contacts and microglia morphodynamics in mice in an activity-dependent context such as the vigilance states.