PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-5 (5)
 

Clipboard (0)
None
Journals
Authors
more »
Year of Publication
Document Types
1.  Stereological assessment of the dorsal anterior cingulate cortex in schizophrenia: absence of changes in neuronal and glial densities 
Aims
The prefrontal and anterior cingulate cortices are implicated in schizophrenia, and many studies have assessed volume, cortical thickness, and neuronal densities or numbers in these regions. Available data however are rather conflicting and no clear cortical alteration pattern has been established. Changes in oligodendrocytes and white matter have been observed in schizophrenia, introducing a hypothesis about a myelin deficit as a key event in disease development.
Methods
We investigated the dorsal anterior cingulate cortex (dACC) in 13 males with schizophrenia and 13 age- and gender-matched controls. We assessed stereologically the dACC volume, neuronal and glial densities, total neuron and glial numbers, and glia/neuron (GNI) ratios in both layers II-III and V-VI.
Results
We observed no differences in neuronal or glial densities. No changes were observed in dACC cortical volume, total neuron numbers, and total glial numbers in schizophrenia. This contrasts with previous findings and suggests that the dACC may not undergo as severe changes in schizophrenia as is generally believed. However, we observed higher glial densities in layers V-VI than in layers II-III in both controls and patients with schizophrenia, pointing to possible layer-specific effects on oligodendrocyte distribution during development.
Conclusions
Using rigorous stereological methods, we demonstrate a seemingly normal cortical organization in an important neocortical area for schizophrenia, emphasizing the importance of such morphometric approaches in quantitative neuropathology. We discuss the significance of subregion- and layer-specific alterations in the development of schizophrenia, and the discrepancies between post-mortem histopathological studies and in vivo brain imaging findings in patients.
doi:10.1111/j.1365-2990.2012.01296.x
PMCID: PMC3508088  PMID: 22860626
dysmyelination; oligodendrocytes; white matter; morphology; cytoarchitecture; myelin
2.  The relationship between cerebral amyloid angiopathy and cortical microinfarcts in brain ageing and Alzheimer’s disease 
Aims
Cerebral amyloid angiopathy (CAA) represents the deposition of amyloid β protein (Aβ) in the meningeal and intracerebral vessels. It is often observed as an accompanying lesion of Alzheimer’s disease (AD) or in the brain of elderly individuals even in the absence of dementia. CAA is largely age-dependent. In subjects with severe CAA a higher frequency of vascular lesions has been reported. The goal of our study was to define the frequency and distribution of CAA in a one-year autopsy population (91 cases) from the Department of Internal Medicine, Rehabilitation, and Geriatrics, Geneva.
Materials and methods
Five brain regions were examined, including the hippocampus, and the inferior temporal, frontal, parietal, and occipital cortex, using an antibody against Aβ, and simultaneously assessing the severity of AD-type pathology with Braak stages for neurofibrillary tangles identified with an anti-tau antibody. In parallel, the relationships of CAA with vascular brain lesions were established.
Results
CAA was present in 53.8% of the studied population, even in cases without AD (50.6%). The strongest correlation was seen between CAA and age, followed by the severity of amyloid plaques deposition. Microinfarcts were more frequent in cases with CAA; however, our results did not confirm a correlation between these parameters.
Conclusion
The present data show that CAA plays a role in the development of microvascular lesions in the aging brain, but cannot be considered as the most important factor in this vascular pathology, suggesting that other mechanisms also contributes importantly to the pathogenesis of microvascular changes.
doi:10.1111/nan.12003
PMCID: PMC3637988  PMID: 23163235
amyloid angiopathy; cortical microinfarcts; Alzheimer’s disease; vascular; neuropathology; immunohistochemistry
3.  Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates 
Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal, and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging (MRI) usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum (CSP), signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces, and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology, and pathogenesis of CTE and Alzheimer’s disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP, and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.
doi:10.1111/j.1365-2990.2011.01186.x
PMCID: PMC3166385  PMID: 21696410
chronic traumatic encephalopathy; traumatic brain injuries; boxing; contact sports; Alzheimer’s disease; frontotemporal dementia; amyotrophic lateral sclerosis
4.  Neuropathological analysis of lacunes and microvascular lesions in late-onset depression 
Aims
Previous neuropathological studies documented that small vascular and microvascular pathology is associated with cognitive decline. More recently, we showed that thalamic and basal ganglia lacunes are associated with post-stroke depression and may affect emotional regulation. The present study examines whether this is also the case for late-onset depression.
Methods
We performed a detailed analysis of small macrovascular and microvascular pathology in the postmortem brains of 38 patients with late-onset major depression (LOD) and 29 healthy elderly controls. A clinical diagnosis of LOD was established while the subjects were alive using the DSM-IV criteria. Additionally, we retrospectively reviewed all charts for the presence of clinical criteria of vascular depression. Neuropathological evaluation included bilateral semiquantitative assessment of lacunes, deep white matter and periventricular demyelination, cortical microinfarcts and both focal and diffuse gliosis. The association between vascular burden and LOD was investigated using Fisher’s exact test and univariate and multivariate logistic regression models.
Results
Neither the existence of lacunes nor the presence of microvascular ischaemic lesions was related to occurrence of LOD. Similarly, there was no relationship between vascular lesion scores and LOD. This was also the case within the subgroup of LOD patients fulfilling the clinical criteria for vascular depression.
Conclusions
Our results challenge the vascular depression hypothesis by showing that neither deep white matter nor periventricular demyelination is associated with LOD. In conjunction with our previous observations in stroke patients, they also imply that the impact of lacunes on mood may be significant solely in the presence of acute brain compromise.
doi:10.1111/j.1365-2990.2010.01101.x
PMCID: PMC2962688  PMID: 20609111
brain ischaemia; elderly; mood; neuropathology; vascular depression
5.  Annotation - Does Alzheimer's disease begin in the brainstem? 
Although substantial evidence indicates that the progression of pathological changes of the neuronal cytoskeleton is crucial in determining the severity of dementia in Alzheimer's disease (AD), the exact causes and evolution of these changes, the initial site at which they begin, and the neuronal susceptibility levels for their development are poorly understood. The current clinical criteria for diagnosis of AD are focused mostly on cognitive deficits produced by dysfunction of hippocampal and high-order neocortical areas, whereas non-cognitive, behavioural, and psychological symptoms of dementia such as disturbances in mood, emotion, appetite, and wake-sleep cycle, confusion, agitation, and depression, have been less considered. The early occurrence of these symptoms suggests brainstem involvement, and more specifically of the serotonergic nuclei. In spite of the fact that the Braak staging system and NIA-RI criteria do not include their evaluation, several recent reports drew attention to the possibility of selective and early involvement of raphe nuclei, particularly the dorsal raphe nucleus (DRN), in the pathogenesis of AD. Based on these findings of differential susceptibility and anatomical connectivity, a novel pathogenetic scheme of AD progression was proposed. Although the precise mechanisms of neurofibrillary degeneration still await elucidation, we speculated that cumulative oxidative damage may be the main cause of DRN alterations, as the age is the main risk factor for sporadic AD. Within such a framework, β–amyloid production is considered only as one of the factors (although a significant one in familial cases) that promotes molecular series of events underlying AD-related neuropathological changes.
doi:10.1111/j.1365-2990.2009.01038.x
PMCID: PMC2787819  PMID: 19682326
aging; Alzheimer's disease; behavioural and psychological symptoms; cerebrospinal fluid; dorsal raphe nucleus; early diagnosis; fetal brain development; neurofibrillary degeneration; serotonin; tau protein

Results 1-5 (5)