S100b Level of Post Mortem Cerebrospinal Fluid and Serum in Blunt Head Trauma Cases

Lipid metabolism is clearly associated to Parkinson’s disease (PD). Although lipid homeostasis has been widely studied in multiple animal and cellular models, as well as in blood derived from PD individuals, the cerebrospinal fluid (CSF) lipidomic profile in PD remains largely unexplored. In this study, we characterized the post-mortem CSF lipidomic imbalance between neurologically intact controls (n = 10) and PD subjects (n = 20). The combination of dual extraction with ultra-performance liquid chromatography-electrospray ionization quadrupole-time-of-flight mass spectrometry (UPLC-ESI-qToF-MS/MS) allowed for the monitoring of 257 lipid species across all samples. Complementary multivariate and univariate data analysis identified that glycerolipids (mono-, di-, and triacylglycerides), saturated and mono/polyunsaturated fatty acids, primary fatty amides, glycerophospholipids (phosphatidylcholines, phosphatidylethanolamines), sphingolipids (ceramides, sphingomyelins), N-acylethanolamines and sterol lipids (cholesteryl esters, steroids) were significantly increased in the CSF of PD compared to the control group. Interestingly, CSF lipid dyshomeostasis differed depending on neuropathological staging and disease duration. These results, despite the limitation of being obtained in a small population, suggest extensive CSF lipid remodeling in PD, shedding new light on the deployment of CSF lipidomics as a promising tool to identify potential lipid markers as well as discriminatory lipid species between PD and other atypical parkinsonisms.

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Diffuse Axonal Injury in Infants With Nonaccidental Craniocerebral Trauma

Archives of Pathology & Laboratory Medicine ◽

10.5858/1999-123-0146-daiiiw ◽

1999 ◽

Vol 123 (2) ◽

pp. 146-151 ◽

Cited By ~ 2

Author(s):

Aaron M. Gleckman ◽

Michael D. Bell ◽

Richard J. Evans ◽

Thomas W. Smith

Keyword(s):

Head Trauma ◽

Axonal Injury ◽

Diffuse Axonal Injury ◽

Craniocerebral Trauma ◽

Shaken Baby Syndrome ◽

Normal Brain ◽

Accurate Identification ◽

Blunt Head Trauma ◽

Hematoxylin Eosin ◽

Axonal Swellings

Abstract Objective.—Accurate identification of diffuse axonal injury is important in the forensic investigation of infants who have died from traumatic brain injury. β-Amyloid precursor protein (β-APP) immunohistochemical staining is highly sensitive in identifying diffuse axonal injury. However, the effectiveness of this method in brain-injured infants has not been well established. The present study was undertaken to assess the utility of β-APP immunohistochemistry in detecting diffuse axonal injury in infants with either shaken baby syndrome or blunt head trauma. Materials and Methods.—Archival formalin-fixed, paraffin-embedded blocks from infants (<1 year old) with shaken baby syndrome (7 cases) and blunt head trauma (3) and blocks from 7 control cases that included nontraumatic cerebral edema (1), acute hypoxic-ischemic encephalopathy (1), and normal brain (5) were immunostained for β-APP. A semiquantitative assessment of the severity of axonal staining was made. Corresponding hematoxylin-eosin–stained sections were examined for the presence of axonal swellings. Results.—Immunostaining for β-APP identified diffuse axonal injury in 5 of 7 infants with shaken baby syndrome and 2 of 3 infants with blunt head trauma. Immunoreactive axons were easily identified and were present in the majority of the sections examined. By contrast, hematoxylin-eosin staining revealed axonal swellings in only 3 of 7 infants with shaken baby syndrome and 1 of 3 infants with blunt head trauma. Most of these sections had few if any visible axonal swellings, which were often overlooked on initial review of the slides. No β-APP immunoreactivity was observed in any of the 7 control cases. Conclusions.—Immunostaining for β-APP can easily and reliably identify diffuse axonal injury in infants younger than 1 year and is considerably more sensitive than routine hematoxylin-eosin staining. We recommend its use in the forensic evaluation of infants with fatal craniocerebral trauma.

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Ante Mortem Cerebrospinal Fluid Levels of Calsyntenin-1 and Neurexin-2a Reflect Post-Mortem TDP-43 Pathology in a Pathological Cohort of Frontotemporal Lobar Degeneration

10.21203/rs.3.rs-885718/v1 ◽

2021 ◽

Author(s):

Alba Cervantes-González ◽

David J Irwin ◽

Daniel Alcolea ◽

Corey T McMillan ◽

Alice Chen-Plotkin ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Frontotemporal Lobar Degeneration ◽

Neurofibrillary Tangle ◽

Surrogate Marker ◽

Quantitative Measure ◽

Synaptic Proteins ◽

Analysis Of Covariance ◽

Early Event ◽

Post Mortem ◽

Csf Levels

Abstract Background. Frontotemporal dementia (FTD) clinical diagnosis is challenged by the variable correspondence between the clinical syndrome and underlying neuropathological changes, the phenotypic overlap with Alzheimer's disease (AD) and the lack of pathophysiologic diagnostic biomarkers. As synapse degeneration is an early event in pathological frontotemporal lobar degeneration (FTLD), a surrogate marker of synapse loss could be used to monitor early pathologic changes. The aim of this study was to evaluate the relationship of antemortem cerebrospinal fluid (CSF) levels of 9 synaptic proteins with postmortem global tau and TDP-43 burden in a neuropathological FTLD cohort. Methods. We included patients with a neuropathological confirmation of FTLD-Tau (n=24, mean age-at-CSF 67 years+/-11), FTLD-TDP (n=25, 66 years+/-9) or AD (n=25, 73 years+/-6) as well as cognitively normal controls (n=35, 69 years+/-7) from the Penn FTD Center and ADRC. A subset of 39 FTLD patients presented without AD comorbidity (neurofibrillary tangle score of B0/B1 according to the NIA-AA classification) and 18 AD patients presented without TDP-43 comorbidity. We quantified the synaptic panel in antemortem CSF by targeted mass spectrometry using isotopically-labeled peptides as internal standards. We used a semi-quantitative measure of tau and TDP-43 inclusions to quantify pathological burden across 16 brain regions. Statistical methods included Spearman rank correlations, one-way analysis of covariance (controlling for sex and age-at-CSF), linear regression (controlling for age-at-death) and receiver-operating characteristic curves. Result. CSF calsyntenin-1 and neurexin-2a were correlated in all patient groups (rs=.55 to .88). In FTLD-TDP, we observed low antemortem CSF levels of calsyntenin-1 and neurexin-2a compared to AD (.72-fold, p=.001, .77-fold, p=.04, respectively) and controls (.80-fold, p=.02, .78-fold, p=.02, respectively), which were inversely associated with post-mortem global TDP-43 burden (regression r2=.36, p=.04 and r2=.35, p=.04, respectively). Neurexin-2a showed 75.0% (95% CI 60-88) accuracy to discriminate FTLD-TDP from controls. Calsyntenin-1 showed 75.1% (95% CI 62-87) accuracy to discriminate FTLD-TDP from AD. None of the synaptic proteins were altered in FTLD-Tau compared to controls (0.79 to 1.12-fold, p>.12) or associated with post-mortem global tau burden (r2=.12, p=.36). Comorbidity had a limited effect on these findings. Conclusion. CSF calsyntenin-1 and neurexin-2a have potential as objective measures of TDP-43-mediated degeneration in FTLD.

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