Acta neuropathologica
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Acta neuropathologica · Oct 2005
Historical ArticleSporadic cerebral amyloid angiopathy: pathology, clinical implications, and possible pathomechanisms.
Cerebral amyloid angiopathy (CAA) was observed for the first time nearly 100 years ago and systematically described in 1938. It is a common finding in elderly individuals, defined by beta-amyloid peptide (Abeta) depositions in cerebral blood vessels, and associated with Alzheimer's disease (AD). A variety of genetic mutations cause hereditary forms of CAA; in this review, however, only the sporadic variant of CAA is considered. ⋯ Both APOE-epsilon4 and APOE-epsilon2 are risk factors for CAA, while only APOE-epsilon2 increases the risk for hemorrhage in CAA. Although the role of CAA as an independent risk factor for cognitive decline is unclear, severe CAA is likely to lower the threshold for clinically overt dementia in neurodegenerative diseases. As for the origin of Abeta in CAA, it may be both produced by smooth muscle cells (vessel wall) and derived from neurons in the course of perivascular drainage.
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Acta neuropathologica · Sep 2005
Alzheimer's disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy.
Cerebral amyloid angiopathy (CAA) is defined by beta-amyloid peptide (Abeta) depositions in cerebral vessels and is associated with Alzheimer's disease (AD). The relationship between sporadic CAA and AD, and the origin of Abeta in CAA are poorly understood. The aim of our study was to investigate the relationship between CAA and AD. ⋯ In concordance with other studies, the severity of both AD pathology and CAA showed a low, but significant correlation. This correlation, however, was only caused by the significant increase of occipital CAA with increasing AD pathology (P<0.01), and was independent of APOE genotype. Our results suggest that progressing AD pathology not only increases the severity of CAA, but also shifts its topographical distribution towards the occipital cortex.
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Acta neuropathologica · Sep 2005
Editorial Biography Historical ArticleAnnouncing the winner of the 2005 Kurt Jellinger Prize.
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Acta neuropathologica · Aug 2005
Comparative StudyRedox system expression in the motor neurons in amyotrophic lateral sclerosis (ALS): immunohistochemical studies on sporadic ALS, superoxide dismutase 1 (SOD1)-mutated familial ALS, and SOD1-mutated ALS animal models.
Peroxiredoxin-ll (Prxll) and glutathione peroxidase-l (GPxl) are regulators of the redox system that is one of the most crucial supporting systems in neurons. This system is an antioxidant enzyme defense system and is synchronously linked to other important cell supporting systems. To clarify the common self-survival mechanism of the residual motor neurons affected by amyotrophic lateral sclerosis (ALS), we examined motor neurons from 40 patients with sporadic ALS (SALS) and 5 patients with superoxide dismutase 1 (SOD1)-mutated familial ALS (FALS) from two different families (frame-shift 126 mutation and A4 V) as well as four different strains of the SOD1-mutated ALS models (H46R/G93A rats and G1H/G1L-G93A mice). ⋯ In the ALS animal models, as in the human diseases, certain residual motor neurons showed overexpression of Prxll/GPxl during their clinical courses. At the terminal stage of ALS, however, a disruption of this common Prxll/GPxl-overexpression mechanism in neurons was observed. These findings lead us to the conclusion that the residual ALS neurons showing redox system up-regulation would be less susceptible to ALS stress and protect themselves from ALS neuronal death, whereas the breakdown of this redox system at the advanced disease stage accelerates neuronal degeneration and/or the process of neuronal death.
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Acta neuropathologica · Aug 2005
Evaluation of the apoptosis-related proteins of the BCL-2 family in the traumatic penumbra area of the rat model of cerebral contusion, treated by hyperbaric oxygen therapy: a quantitative immunohistochemical study.
The growth and progression of traumatic brain injury (TBI) lesions depend significantly on developments in the traumatic penumbra area, perilesional region, where delayed neuronal death occurs. Recent data supports the important role of apoptosis in delayed cell death in TBI. Previously we demonstrated a significant reduction of apoptosis in traumatic penumbra in animals treated by hyperbaric oxygen (HBO). ⋯ We concluded that the apoptotic mechanisms are important in delayed cell death in TBI and that post-traumatic hypoxemia increases the intensity of apoptosis, probably through a decrease in Bcl-2 and Bcl-xL expression which normally repress apoptosis. The beneficial effect of HBO treatment in our model of brain contusion correlates well with the increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) following treatment and the appropriate decrease in the extent of apoptosis. In light of these results, the usage of HBO is justified as neuroprotective treatment in TBI.