105
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Assessment of Alzheimer’s disease (AD)-related neurofibrillary pathology requires a procedure that permits a sufficient differentiation between initial, intermediate, and late stages. The gradual deposition of a hyperphosphorylated tau protein within select neuronal types in specific nuclei or areas is central to the disease process. The staging of AD-related neurofibrillary pathology originally described in 1991 was performed on unconventionally thick sections (100 μm) using a modern silver technique and reflected the progress of the disease process based chiefly on the topographic expansion of the lesions. To better meet the demands of routine laboratories this procedure is revised here by adapting tissue selection and processing to the needs of paraffin-embedded sections (5–15 μm) and by introducing a robust immunoreaction (AT8) for hyperphosphorylated tau protein that can be processed on an automated basis. It is anticipated that this revised methodological protocol will enable a more uniform application of the staging procedure.

          Related collections

          Most cited references85

          • Record: found
          • Abstract: found
          • Article: not found

          Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease.

          We studied the accumulation of neurofibrillary tangles (NFTs) and senile plaques (SPs) in 10 Alzheimer's disease patients who had been examined during life. We counted NFTs and SPs in 13 cytoarchitectural regions representing limbic, primary sensory, and association cortices, and in subcortical neurotransmitter-specific areas. The degree of neuropathologic change was compared with the severity of dementia, as assessed by the Blessed Dementia Scale and duration of illness. We found that (1) the severity of dementia was positively related to the number of NFTs in neocortex, but not to the degree of SP deposition; (2) NFTs accumulate in a consistent pattern reflecting hierarchic vulnerability of individual cytoarchitectural fields; (3) NFTs appeared in the entorhinal cortex, CA1/subiculum field of the hippocampal formation, and the amygdala early in the disease process; and (4) the degree of SP deposition was also related to a hierarchic vulnerability of certain brain areas to accumulate SPs, but the pattern of SP distribution was different from that of NFT.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease.

            To determine the spatiotemporal mapping of neurofibrillary degeneration (NFD) in normal aging and the different stages of AD. The pathophysiologic significance of AD lesions, namely amyloid plaques and neurofibrillary tangles, is still unclear, especially their interrelationship and their link with cognitive impairment. The study included 130 patients of various ages and different cognitive statuses, from nondemented control subjects (n = 60, prospective study) to patients with severe definite AD. Paired helical filaments (PHF)-tau and Abeta were used as biochemical and histologic markers of NFD and amyloid plaques, respectively. NFD with PHF-tau was systematically present in variable amounts in the hippocampal region of nondemented patients age >75 years. When NFD was found in other brain areas, it was always along a stereotyped, sequential, hierarchical pathway. The progression was categorized into 10 stages according to the brain regions affected: transentorhinal cortex (S1), entorhinal (S2), hippocampus (S3), anterior temporal cortex (S4), inferior temporal cortex (S5), medium temporal cortex (S6), polymodal association areas (prefrontal, parietal inferior, temporal superior) (S7), unimodal areas (S8), primary motor (S9a) or sensory (S9b, S9c) areas, and all neocortical areas (S10). Up to stage 6, the disease could be asymptomatic. In all cases studied here, stage 7 individuals with two polymodal association areas affected by tau pathologic states were cognitively impaired. The relationship between NFD and Alzheimer-type dementia, and the criteria for a biochemical diagnosis of AD, are documented, and an association between AD and the extent of NFD in defined brain areas is shown.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease.

              The distribution of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) was mapped in 39 cortical areas of 11 brains of patients with Alzheimer's disease (AD). Whole hemisphere blocks were embedded in polyethylene glycol (Carbowax), sectioned coronally, and stained with thioflavin S and thionin. The densities of NFTs and NPs were assessed using a numerical rating scale for each area. Scores were grouped by type of cortex and by lobe for statistical analysis. Highly significant differences were obtained. For example, limbic periallocortex and allocortex had more NFTs than any other type of cortex. In descending order, the density of NFTs was as follows: periallocortex (area 28) greater than allocortex (subiculum/CA1 zones of hippocampal formation, area 51) greater than corticoid areas (accessory basal nucleus of amygdala, nucleus basalis of Meynert) greater than proisocortex (areas 11, 12, 24, 23, anterior insula, 38, 35) greater than nonprimary association cortex (32, 46, superior temporal sulcus, 40, 39, posterior parahippocampal cortex, 37, 36) greater than primary sensory association cortex (7, 18, 19, 22, 21, 20) greater than agranular cortex (44-5, 8, 6, 4) greater than primary sensory cortex (41-2, 3-1-2, 17). The laminar distribution of NFTs tended to be selective, involving primarily layers III and V of association areas and layers II and IV of limbic periallocortex. There were far more NFTs in both limbic and temporal lobes than in frontal, parietal, and occipital lobes. In general, NPs were more evenly distributed throughout the cortex, with the exceptions of limbic periallocortex and allocortex, which had notably fewer NPs than other cortical areas. Temporal and occipital lobes had the highest NP densities, limbic and frontal lobes had the lowest, and parietal lobe was intermediate. No significant left-right hemispheric differences for NFT or NP densities were found across the population, and there was no relationship between duration of illness and densities of NFTs or NPs. The regional and laminar distribution of NFTs (and, to a lesser degree, that of NPs) suggests a consistent pattern of vulnerability within the cerebral cortices that seems correlated to the hierarchies of cortico-cortical connections. The higher-order association cortices, especially those in the anterior and ventromedial sectors of temporal lobe, are the most vulnerable, while other cortices appear less vulnerable to a degree commensurate with their connectional "distance" (i.e., synapses removed) from the limbic areas.
                Bookmark

                Author and article information

                Contributors
                +49-69-63016900 , +49-69-63016425 , Braak@em.uni-frankfurt.de
                Journal
                Acta Neuropathol
                Acta Neuropathol
                Acta Neuropathologica
                Springer-Verlag (Berlin/Heidelberg )
                0001-6322
                1432-0533
                12 August 2006
                12 August 2006
                2006
                : 112
                : 389-404
                Affiliations
                [ ]Institute for Clinical Neuroanatomy, J.W. Goethe University Clinic, Theodor Stern Kai 7, 60590 Frankfurt/Main, Germany
                [ ]Institute of Clinical Medicine, Pathology, Kuopio University and University Hospital, Harjulantie 1, P.O. Box 1627, 70211 Kuopio, Finland
                [ ]Institute of Neuropathology, Ludwig Maximilians University, 81377 Munich, Germany
                [ ]Clinic for Psychiatry and Neurology Winnenden, 71364 Winnenden, Germany
                Article
                127
                10.1007/s00401-006-0127-z
                3906709
                16906426
                aafe2670-f519-42b1-bfb4-6f7adc62fd9f
                © Springer-Verlag 2006
                Categories
                Methods Report
                Custom metadata
                © Springer-Verlag 2006

                Comments

                Comment on this article