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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

Confocal microscopy of sections double stained with an anti-PHF-tau antibody (red) and Thioflavine-S (TS, green), which labels PHF-tau forming NFT. (A,B), (D,E), (G,H), and (J,K) pairs of confocal images from the same section and field in the CA1 hippocampal region of AD patient P1, P7, P4, and P3, respectively. Panels (C,F,I,L) were obtained by combining these images (A) and (B), (D) and (E), (G) and (H), (J) and (K), respectively. Note that type I PHF-tau-ir neurons (one asterisk) were free of NFT, whereas type II neurons (two asterisks) contained NFT (arrows). Scale bar: (A–C), 21 μm; (D–F), 24 μm; (G–L), 31.5 μm.
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Figure 3: Confocal microscopy of sections double stained with an anti-PHF-tau antibody (red) and Thioflavine-S (TS, green), which labels PHF-tau forming NFT. (A,B), (D,E), (G,H), and (J,K) pairs of confocal images from the same section and field in the CA1 hippocampal region of AD patient P1, P7, P4, and P3, respectively. Panels (C,F,I,L) were obtained by combining these images (A) and (B), (D) and (E), (G) and (H), (J) and (K), respectively. Note that type I PHF-tau-ir neurons (one asterisk) were free of NFT, whereas type II neurons (two asterisks) contained NFT (arrows). Scale bar: (A–C), 21 μm; (D–F), 24 μm; (G–L), 31.5 μm.

Mentions: Using a variety of silver and immunohistochemical staining techniques, the pathological changes of the immunoreactive neurons were classified and a morphological series was established to reflect the sequence of changes believed to be experienced by the individual nerve cell as the disease progresses (Braak et al., 1994). In general, early stages are characterized by abnormal delicate fibrillary inclusions within affected neurons. These fibers aggregate into large bundles that finally fill the entire neuronal cytoplasm as classic NFT. In the present work, we classified PHF-tau-ir neurons as type I or II, based on previous studies (Bancher et al., 1989 and Braak et al., 1994). In sections immunocytochemically stained with the anti-PHF-tau antibody, numerous neurons were labeled in all cortical areas of the hippocampal formation and adjacent cortex examined (Figure 1). Type I corresponds to Stage 0–1 in Bancher et al. (1989) and Group 1–2 of Braak et al. (1994), while type II corresponds to Stage 2–3 of Bancher et al. (1989) and Group 3–5 of Braak et al. (1994). The type I pattern was characterized by the diffuse cytoplasmic staining (with no NFT: Figures 2 and 3) of neurons with a normal morphology, but with dendrites and proximal axons that were often strongly stained, displaying Golgi-like labeling. In neurons with a type II pattern, the amount of somatic cytoplasm occupied by the NFT varied (Figures 2 and 3). The dendritic arbor of the neurons had relatively little NFT and it usually displayed numerous dendritic processes. Neurons whose cytoplasm was full of NFT have very few dendritic processes, suggesting they were undergoing neuronal atrophy.


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)

Confocal microscopy of sections double stained with an anti-PHF-tau antibody (red) and Thioflavine-S (TS, green), which labels PHF-tau forming NFT. (A,B), (D,E), (G,H), and (J,K) pairs of confocal images from the same section and field in the CA1 hippocampal region of AD patient P1, P7, P4, and P3, respectively. Panels (C,F,I,L) were obtained by combining these images (A) and (B), (D) and (E), (G) and (H), (J) and (K), respectively. Note that type I PHF-tau-ir neurons (one asterisk) were free of NFT, whereas type II neurons (two asterisks) contained NFT (arrows). Scale bar: (A–C), 21 μm; (D–F), 24 μm; (G–L), 31.5 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Confocal microscopy of sections double stained with an anti-PHF-tau antibody (red) and Thioflavine-S (TS, green), which labels PHF-tau forming NFT. (A,B), (D,E), (G,H), and (J,K) pairs of confocal images from the same section and field in the CA1 hippocampal region of AD patient P1, P7, P4, and P3, respectively. Panels (C,F,I,L) were obtained by combining these images (A) and (B), (D) and (E), (G) and (H), (J) and (K), respectively. Note that type I PHF-tau-ir neurons (one asterisk) were free of NFT, whereas type II neurons (two asterisks) contained NFT (arrows). Scale bar: (A–C), 21 μm; (D–F), 24 μm; (G–L), 31.5 μm.
Mentions: Using a variety of silver and immunohistochemical staining techniques, the pathological changes of the immunoreactive neurons were classified and a morphological series was established to reflect the sequence of changes believed to be experienced by the individual nerve cell as the disease progresses (Braak et al., 1994). In general, early stages are characterized by abnormal delicate fibrillary inclusions within affected neurons. These fibers aggregate into large bundles that finally fill the entire neuronal cytoplasm as classic NFT. In the present work, we classified PHF-tau-ir neurons as type I or II, based on previous studies (Bancher et al., 1989 and Braak et al., 1994). In sections immunocytochemically stained with the anti-PHF-tau antibody, numerous neurons were labeled in all cortical areas of the hippocampal formation and adjacent cortex examined (Figure 1). Type I corresponds to Stage 0–1 in Bancher et al. (1989) and Group 1–2 of Braak et al. (1994), while type II corresponds to Stage 2–3 of Bancher et al. (1989) and Group 3–5 of Braak et al. (1994). The type I pattern was characterized by the diffuse cytoplasmic staining (with no NFT: Figures 2 and 3) of neurons with a normal morphology, but with dendrites and proximal axons that were often strongly stained, displaying Golgi-like labeling. In neurons with a type II pattern, the amount of somatic cytoplasm occupied by the NFT varied (Figures 2 and 3). The dendritic arbor of the neurons had relatively little NFT and it usually displayed numerous dendritic processes. Neurons whose cytoplasm was full of NFT have very few dendritic processes, suggesting they were undergoing neuronal atrophy.

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