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Pericellular innervation of neurons expressing abnormally hyperphosphorylated tau in the hippocampal formation of Alzheimer's disease patients.

Blazquez-Llorca L, Garcia-Marin V, Defelipe J - Front Neuroanat (2010)

Bottom Line: This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons.Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau.These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Circuitos Corticales (Centro de Tecnología Biomédica), Universidad Politécnica de Madrid Madrid, Spain.

ABSTRACT
Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered.

No MeSH data available.


Related in: MedlinePlus

Drawings based on Neurolucida plots made with a 40× objective showing the distribution of PHF-tau-ir neurons showing type I (blue dots) and type II (red dots) staining in the hippocampal formation and adjacent cortex from AD cases. Borders between the different cytoarchitectonic regions are indicated by arrowheads. Scale bar: 1,000 μm.
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Figure 5: Drawings based on Neurolucida plots made with a 40× objective showing the distribution of PHF-tau-ir neurons showing type I (blue dots) and type II (red dots) staining in the hippocampal formation and adjacent cortex from AD cases. Borders between the different cytoarchitectonic regions are indicated by arrowheads. Scale bar: 1,000 μm.

Mentions: Since PHF-tau-ir neurons were also present in control tissue (see Discussion), we plotted all PHF-tau-ir neurons in the hippocampal formation and adjacent cortex from both control (Figure 4) and AD patients (Figure 5). Moreover, we quantified the density of PHF-tau-ir neurons with type I and II staining in the different regions (Figure 6). In general, a lower density of PHF-tau-ir cells was found in control tissue than in that from AD patients in all the fields studied, with the exception of control case C4 in which a similar or higher density than in AD cases was evident in the Sub, CA1, and CA2. The density of PHF-tau-ir neurons varied considerably between different AD patients. For example, while patient P1 was diagnosed at AD stage IV (the most severe stage of all the cases studied), this patient only had the highest density of PHF-tau-ir neurons in the preS when compared with the rest of the control and AD tissue (Figure 6A). Patient P4 had much lower densities in all the hippocampal fields than P3, P6, and P7 patients, even though each was considered as stage AD III (Table 2). In addition, patients P6 and P7 showed a relatively high density of PHF-tau-ir neurons in the DG even though granular cells do not typically develop neurofibrillary lesions (Braak and Braak, 1991). Interestingly, these two patients also suffered from argyrophilic grain disease (AGD), which is a neurodegenerative disease often associated to other neurodegenerative disorders and that is characterized by the presence of argyrophilic grains in several cortical regions. It has been suggested that AGD may enhance the pathological alterations in several neurodegenerative disorders, including AD, particularly in the DG (Thal et al., 2005; Ferrer et al., 2008; Josephs et al., 2008). Thus, the high density of PHF-tau-ir neurons in the DG in cases P6 and P7 might be explained by the co-existence of AGD.


Pericellular innervation of neurons expressing abnormally hyperphosphorylated tau in the hippocampal formation of Alzheimer's disease patients.

Blazquez-Llorca L, Garcia-Marin V, Defelipe J - Front Neuroanat (2010)

Drawings based on Neurolucida plots made with a 40× objective showing the distribution of PHF-tau-ir neurons showing type I (blue dots) and type II (red dots) staining in the hippocampal formation and adjacent cortex from AD cases. Borders between the different cytoarchitectonic regions are indicated by arrowheads. Scale bar: 1,000 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2903190&req=5

Figure 5: Drawings based on Neurolucida plots made with a 40× objective showing the distribution of PHF-tau-ir neurons showing type I (blue dots) and type II (red dots) staining in the hippocampal formation and adjacent cortex from AD cases. Borders between the different cytoarchitectonic regions are indicated by arrowheads. Scale bar: 1,000 μm.
Mentions: Since PHF-tau-ir neurons were also present in control tissue (see Discussion), we plotted all PHF-tau-ir neurons in the hippocampal formation and adjacent cortex from both control (Figure 4) and AD patients (Figure 5). Moreover, we quantified the density of PHF-tau-ir neurons with type I and II staining in the different regions (Figure 6). In general, a lower density of PHF-tau-ir cells was found in control tissue than in that from AD patients in all the fields studied, with the exception of control case C4 in which a similar or higher density than in AD cases was evident in the Sub, CA1, and CA2. The density of PHF-tau-ir neurons varied considerably between different AD patients. For example, while patient P1 was diagnosed at AD stage IV (the most severe stage of all the cases studied), this patient only had the highest density of PHF-tau-ir neurons in the preS when compared with the rest of the control and AD tissue (Figure 6A). Patient P4 had much lower densities in all the hippocampal fields than P3, P6, and P7 patients, even though each was considered as stage AD III (Table 2). In addition, patients P6 and P7 showed a relatively high density of PHF-tau-ir neurons in the DG even though granular cells do not typically develop neurofibrillary lesions (Braak and Braak, 1991). Interestingly, these two patients also suffered from argyrophilic grain disease (AGD), which is a neurodegenerative disease often associated to other neurodegenerative disorders and that is characterized by the presence of argyrophilic grains in several cortical regions. It has been suggested that AGD may enhance the pathological alterations in several neurodegenerative disorders, including AD, particularly in the DG (Thal et al., 2005; Ferrer et al., 2008; Josephs et al., 2008). Thus, the high density of PHF-tau-ir neurons in the DG in cases P6 and P7 might be explained by the co-existence of AGD.

Bottom Line: This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons.Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau.These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Circuitos Corticales (Centro de Tecnología Biomédica), Universidad Politécnica de Madrid Madrid, Spain.

ABSTRACT
Neurofibrillary tangles (NFT) represent one of the main neuropathological features in the cerebral cortex associated with Alzheimer's disease (AD). This neurofibrillary lesion involves the accumulation of abnormally hyperphosphorylated or abnormally phosphorylated microtubule-associated protein tau into paired helical filaments (PHF-tau) within neurons. We have used immunocytochemical techniques and confocal microscopy reconstructions to examine the distribution of PHF-tau-immunoreactive (ir) cells, and their perisomatic GABAergic and glutamatergic innervations in the hippocampal formation and adjacent cortex of AD patients. Furthermore, correlative light and electron microscopy was employed to examine these neurons and the perisomatic synapses. We observed two patterns of staining in PHF-tau-ir neurons, pattern I (without NFT) and pattern II (with NFT), the distribution of which varies according to the cortical layer and area. Furthermore, the distribution of both GABAergic and glutamatergic terminals around the soma and proximal processes of PHF-tau-ir neurons does not seem to be altered as it is indistinguishable from both control cases and from adjacent neurons that did not contain PHF-tau. At the electron microscope level, a normal looking neuropil with typical symmetric and asymmetric synapses was observed around PHF-tau-ir neurons. These observations suggest that the synaptic connectivity around the perisomatic region of these PHF-tau-ir neurons was apparently unaltered.

No MeSH data available.


Related in: MedlinePlus