| 1. |
- Alafuzoff, Irina, et al.
(författare)
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Assessment of beta-amyloid deposits in human brain : a study of the BrainNet Europe Consortium
- 2009
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 117:3, s. 309-320
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Tidskriftsartikel (refereegranskat)abstract
- beta-Amyloid (A-beta) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as iota and alpha synuclein related lesions, also A-beta related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of A-beta, i.e. phase 1 = deposition of A-beta exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of A-beta phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of A-beta-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer's disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the A-beta phase in AD is feasible even in large scale retrospective studies.
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| 2. |
- Pikkarainen, Maria, et al.
(författare)
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Hyperphosphorylated tau in the occipital cortex in aged nondemented subjects
- 2009
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Ingår i: Journal of Neuropathology and Experimental Neurology. - 0022-3069 .- 1554-6578. ; 68:6, s. 653-660
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Tidskriftsartikel (refereegranskat)abstract
- To determine the extent of neurodegeneration of the visual association cortex, we assessed hyperphosphorylated tau-immunoreactive (HPtau-IR) neurofibrillary tangles in Brodmann Areas 18/19 in nondemented and demented subjects. At least occasional HPtau-IR neurofibrillary tangles were seen in 24% of 59 nondemented subjects with ages at death ranging from 42 to 87 years. The incidence increased to 41% in the 32 nondemented subjects who had HPtau-IR pathology in the hippocampal region. Demented subjects with Braak Stages 0 to III and corticobasal degeneration, frontotemporal lobar degeneration with TAR DNA binding protein 43, vascular cognitive impairment, or dementia with Lewy bodies also had HPtau-IR pathology in Brodmann Areas 18/19. These results support the concept that the occipital association area may have enhanced vulnerability to neurodegeneration. Neuropathologic assessment of these areas is, therefore, recommended, particularly in subjects suspected or known to have had mild cognitive impairment. Occasional HPtau-IR lesions were also seen in the medial temporal gyrus. Thus, the question as to whether scattered HPtau-IR lesions in either temporal or occipital cortex indicate a neurodegenerative disease remains unresolved. Further systematic clinicopathologic studies are needed for an understanding of regional susceptibility to neurodegeneration and the significance of scattered HPtau-IR brain lesions.
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| 3. |
- Seppänen, Allan, et al.
(författare)
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Expression of collagen XVII and ubiquitin-binding protein p62 in motor neuron disease
- 2009
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1247, s. 171-177
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Tidskriftsartikel (refereegranskat)abstract
- Collagen involvement in motor neuron disease has been suggested by several earlier studies. Recently, we found collagen XVII to be expressed in locations in the human brain that include those damaged in motor neuron disease. In this study, we examined the extent of motor neuron disease-related changes in the brain of 9 subjects using ubiquitin-binding protein p62/sequestosome 1 (p62) immunohistochemistry. We then assessed whether or not the expression of collagen XVII was altered in relation to the p62 immunoreactive lesions. We found that neuronal collagen XVII expression in motor neuron disease remains similar to that seen in the normal human brain and thus a change in collagen XVII expression is not an immunohistochemically detectable feature of motor neuron disease. We also found that the regional distribution of p62 varied according to clinical presentation: p62 immunoreactive inclusions were found in the frontal cortex, hippocampus and cerebellum only in subjects with a history of psychiatric morbidity. Our study supports the re-definition of motor neuron disease as a multisystem disorder with a wide clinicopathological spectrum, and we advocate addressing psychiatric symptomology in future studies of motor neuron disease.
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