| 1. |
- Alafuzoff, Irina, et al.
(författare)
-
Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions : an inter-laboratory study by the BrainNet Europe consortium
- 2015
-
Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 122:7, s. 957-972
-
Tidskriftsartikel (refereegranskat)abstract
- The BrainNet Europe consortium assessed the reproducibility in the assignment of the type of frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) 43 following current recommendations. The agreement rates were influenced by the immunohistochemical (IHC) method and by the classification strategy followed. p62-IHC staining yielded good uniform quality of stains, but the most reliable results were obtained implementing specific Abs directed against the hallmark protein TDP43. Both assessment of the type and the extent of lesions were influenced by the Abs and by the quality of stain. Assessment of the extent of the lesions yielded poor results repeatedly; thus, the extent of pathology should not be used in diagnostic consensus criteria. Whilst 31 neuropathologists typed 30 FTLD-TDP cases, inter-rater agreement ranged from 19 to 100 per cent, being highest when applying phosphorylated TDP43/IHC. The agreement was highest when designating Type C or Type A/B. In contrast, there was a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist, independent of his/her familiarity with FTLD-TDP pathology, can identify a TDP43-positive FTLD case. The goal should be to state a Type (A, B, C, D) or a mixture of Types (A/B, A/C or B/C). Neuropathologists, other clinicians and researchers should be aware of the pitfalls whilst doing so. Agreement can be reached in an inter-laboratory setting regarding Type C cases with thick and long neurites, whereas the differentiation between Types A and B may be more troublesome.
|
|
| 2. |
- Alafuzoff, Irina, et al.
(författare)
-
Staging of neurofibrillary pathology in Alzheimer's disease : a study of the BrainNet Europe Consortium.
- 2008
-
Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 18:4, s. 484-96
-
Tidskriftsartikel (refereegranskat)abstract
- It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-microm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V-VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I-II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.
|
|
| 3. |
- Geranmayeh, Fatemeh, et al.
(författare)
-
Microglia in gemistocytic astrocytomas
- 2007
-
Ingår i: Neurosurgery. - 0148-396X .- 1524-4040. ; 60:1, s. 159-166
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Although gemistocytic astrocytomas, they behave more aggressively than other astrocytomas. Their proliferative potential is low, and it remains an intriguing question why these tumors are so biologically "successful". They show a high mutation rate of the P53 gene, cytological abnormalities, and frequent perivascular mononuclear infiltrates. Microglial cells, a feature of this astrocytoma variant, are of increasing interest in the context of glioma growth. Methods: We selected 23 tumor biopsies from 201 samples obtained from patients with gemistocytic astrocytomas operated at Mayo Clinic between 1985 and 1998. These tumors were formerly anaylzed for P53 mutations, P53 protein, and proliferative activity (9). Immunolabeling for three microglial markers, including CR3/43, Ki-M1P, and iba1, was performed on adjacent tissue sections. In additions, in situ hybridization for the alpha-chain of the major histocompatibility complex (MHC) Class II molecule recognized by the CR3/43 monoclonal antibody was performed. Results: A high number of microglia was detected in gemistoccytic astrocytomas. More microglia were present if the fraction of gemistocytic tumor cells was high (correlation coefficient = 0.699; P < 0.0002). Interestingly, a number of gemistocytes were immunoreactive for MHC Class II molecules, an observation confirmed by in situ hybridization. Importantly, the higher the number of Class II immunoreactive gemistocytes, the fewer Class II positive microglial cell could be detected (correlation coefficient = -0.5649; P < 0.005). Conclusion: Our results support the view that gemistocytic astrocytomas contain unusually high numbers of microglial cells. We propose that the finding of aberrant MHC Class II expression by gemistocytic tumor cells correlates with a loss of immune-competent MHC Class II-expressing microglia. This may be related to the expecially poor prognosis of gemistocytic astrocytomas for which induction of T cell anergy could provide one explanation.
|
|
| 4. |
- Alafuzoff, Irina, et al.
(författare)
-
Assessment of beta-amyloid deposits in human brain : a study of the BrainNet Europe Consortium
- 2009
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 117:3, s. 309-320
-
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.
|
|
