Doublecortin expression in CD8+ T-cells and microglia at sites of amyloid-β plaques:A potential role in shaping plaque pathology?

Abstract INTRODUCTION: One characteristic of Alzheimer's disease is the formation of amyloid-β plaques, which are typically linked to neuroinflammation and surrounded by inflammatory cells such as microglia and infiltrating immune cells. METHODS: Here, we describe nonneurogenic doublecortin (DCX) positive cells, DCX being generally used as a marker for young immature neurons, at sites of amyloid-β plaques in various transgenic amyloid mouse models and in human brains with plaque pathology. RESULTS: The plaque-associated DCX+ cells were not of neurogenic identity, instead most of them showed coexpression with markers for microglia (ionized calcium-binding adapter molecule 1) and for phagocytosis (CD68 and TREM2). Another subpopulation of plaque-associated DCX+ cells was negative for ionized calcium-binding adapter molecule 1 but was highly positive for the pan-leukocyte marker CD45. These hematopoietic cells were identified as CD3-and CD8-positive and CD4-negative T-cells. DISCUSSION: Peculiarly, the DCX+/ionized calcium-binding adapter molecule 1+ microglia and DCX+/CD8+ T-cells were closely attached, suggesting that these two cell types are tightly interacting and that this interaction might shape plaque pathology

Motor deficits following dorsal corticospinal tract transection in rats: voluntary versus skilled locomotion readouts

Following spinal cord injury, severe deficits result from damages to ascending and descending tracts, such as the corticospinal tract (CST) which is highly relevant for the motor execution in humans. Unfortunately, no curative treatment is available and intensive efforts are deployed in animal models, such as the CST transection model, to identify interventions providing functional regeneration after spinal cord injury. The CatWalk XT is a system for multi-parameter gait analysis of voluntary locomotion. In this study, the performance of the CatWalk XT for monitoring of functional deficits associated with dorsal CST lesion in rats was compared to skilled locomotion tests. Motor deficits associated with dorsal CST transection could be reliably monitored over seven weeks based on skilled locomotion testing, i.e. Horizontal Ladder Walk and Grid Walk. The collateral lesion to the overlaying gracile and cuneate funiculi occurring during dorsal CST transection resulted in slight hyposensitivity and proprioceptive deficit, which likely contributed to the lowered performance in skilled locomotion. In contrast, parameters of voluntary locomotion were not significantly affected by dorsal CST transection. Finally, an abnormal adduction reflex was detected immediately after lesion of the CST and could be conveniently used to confirm successful CST lesion in rats of experimental groups. The functional relevance of the dorsal CST in locomotion of rats is not as prominent as compared to in humans and thus challenging the motor execution is mandatory to reliably investigate CST function. A detailed analysis of voluntary walking using the CatWalk XT is not adequate to detect deficits following dorsal CST lesion in rats

Nontraumatic spinal cord injury at the neurological intensive care unit: spectrum, causes of admission and predictors of mortality

Objective: Nontraumatic spinal cord injuries (NTSCIs) form a heterogeneous group of diseases, which may evolve into a life-threatening condition. We sought to characterize spectrum, causes of admission and predictors of death in patients with NTSCI treated at the neurological intensive care unit (NICU). Methods: We performed a retrospective observational analysis of NTSCI cases treated at a tertiary care center between 2001 and 2013. Among the 3937 NICU admissions were 93 patients with NTSCI (2.4%). Using multivariate logistic regression analysis, we examined predictors of mortality including demographics, etiology, reasons for admission and GCS/SAPS (Glasgow Coma Scale/Simplified Acute Physiology Score) scores. Results: Infectious and inflammatory/autoimmune causes made up 50% of the NTSCI cases. The most common reasons for NICU admission were rapidly progressing paresis (49.5%) and abundance of respiratory insufficiency (26.9%). The mortality rate was 22.6% and 2.5-fold higher than in the cohort of all other patients treated at the NICU. Respiratory insufficiency as the reason for NICU admission [odds ratio (OR) 4.97, 95% confidence interval (CI) 1.38–17.9; p < 0.01], high initial SAPS scores (OR 1.04; 95% CI 1.003–1.08; p = 0.04), and the development of acute kidney injury throughout the stay (OR 7.25, 1.9–27.5; p = 0.004) were independent risk factors for NICU death. Conclusions: Patients with NTSCI account for a subset of patients admitted to the NICU and are at risk for adverse outcome. A better understanding of predisposing conditions and further knowledge of management of critically ill patients with NTSCI is mandatory

Immune cell interactions in amyloid‐beta plaque pathology

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the Western world characterized by a progressive loss of cognitive functions leading to dementia. Besides others, AD is characterized by the formation of amyloid-beta plaques, which often co-localize with increased neuroinflammation, ie activation of brain resident glial cells, in particular microglia, as well as infiltrating peripheral immune cells. The function and interaction of peripheral immune cells with the brains microglia are so far not fully understood. By serendipity, we observed doublecortin (DCX; generally used as a marker for young immature neurons) positive cells located at sites of amyloid-beta plaques in various transgenic amyloid mouse models and in human AD specimen

Immune cell interactions in amyloid‐beta plaque pathology

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the Western world characterized by a progressive loss of cognitive functions leading to dementia. Besides others, AD is characterized by the formation of amyloid-beta plaques, which often co-localize with increased neuroinflammation, ie activation of brain resident glial cells, in particular microglia, as well as infiltrating peripheral immune cells. The function and interaction of peripheral immune cells with the brains microglia are so far not fully understood. By serendipity, we observed doublecortin (DCX; generally used as a marker for young immature neurons) positive cells located at sites of amyloid-beta plaques in various transgenic amyloid mouse models and in human AD specimen