Mass Spectrometry Archives - The NOMIS Foundation

Structural and functional changes in cortical and subcortical regions have been reported in behavioral variant frontotemporal dementia (bvFTD), however, a multimodal approach may provide deeper insights into the neural correlates of neuropsychiatric symptoms. In this multicenter study, we measured cortical thickness (CTh) and subcortical volumes to identify structural abnormalities in 37 bvFTD patients, and 37 age- and sex-matched healthy controls. For seed regions with significant structural changes, whole-brain functional connectivity (FC) was examined in a sub-cohort of N = 22 bvFTD and N = 22 matched control subjects to detect complementary alterations in brain network organization. To explore the functional significance of the observed structural and functional deviations, correlations with clinical and neuropsychological outcomes were tested where available. Significantly decreased CTh was observed in the bvFTD group in caudal middle frontal gyrus, left pars opercularis, bilateral superior frontal and bilateral middle temporal gyrus along with subcortical volume reductions in bilateral basal ganglia, thalamus, hippocampus, and amygdala. Resting-state functional magnetic resonance imaging showed decreased FC in bvFTD between: dorsal striatum and left caudal middle frontal gyrus; putamen and fronto-parietal regions; pallidum and cerebellum. Conversely, bvFTD showed increased FC between: left middle temporal gyrus and paracingulate gyrus; caudate nucleus and insula; amygdala and parahippocampal gyrus. Additionally, cortical thickness in caudal, lateral and superior frontal regions as well as caudate nucleus volume correlated negatively with apathy severity scores of the Neuropsychiatry Inventory Questionnaire. In conclusion, multimodal structural and functional imaging indicates that fronto-striatal regions have a considerable influence on the severity of apathy in bvFTD. © 2023, The Author(s).

Cerebrospinal fluid (CSF) proteins and their structures have been implicated in aging and neurodegenerative diseases. In the present study, we used limited proteolysis–mass spectrometry (LiP–MS) to screen for new aging-associated changes in the CSF proteome using a modified analysis. We found 38 protein groups that change in abundance with aging, predominantly immunoglobulins of the IgM subclass. We discovered six high-confidence candidates that underwent structural changes with aging, of which Kng1, Itih2, Lp-PLA2 and 14-3-3 proteins have binding partners or chemical forms known previously to change in the brains of patients with Alzheimer’s disease. Orthogonal validation by western blotting identified that the LiP–MS hit Cd5l forms a covalent complex with IgM in mouse and human CSF, the abundance of which increases with aging. In human CSF, SOMAmer probe signals for all six LiP–MS hits were associated with cognitive function and/or biomarkers of neurodegeneration, especially 14-3-3 proteins YWHAB and YWHAZ. Together, our findings show that LiP–MS can uncover age-related structural changes in CSF with relevance to neurodegeneration.

Publications in Mass Spectrometry by NOMIS researchers

Fronto-striatal alterations correlate with apathy severity in behavioral variant frontotemporal dementia

Limited proteolysis–mass spectrometry reveals aging-associated changes in cerebrospinal fluid protein abundances and structures