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Midbrain catecholaminergic neurons co-express α-synuclein and tau in progressive supranuclear palsy.

Erro Aguirre ME, Zelaya MV, Sánchez Ruiz de Gordoa J, Tuñón MT, Lanciego JL - Front Neuroanat (2015)

Bottom Line: Deposits α-synuclein in the form of typical Lewy bodies (LBs) were only found in two PSP cases (8%) that fulfilled the clinical subtype of PSP known as Richardson's syndrome (RS).Tau protein co-aggregate with α-synuclein in catecholaminergic neurons of PSP brains suggesting a synergistic interaction between the two proteins.This is in keeping with the current view of neurodegenerative disorders as "misfolded protein diseases".

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Complejo Hospitalario de Navarra Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) Pamplona, Spain.

ABSTRACT

Objective: To analyze the frequency and distribution of α-synuclein deposits in progressive supranuclear palsy (PSP).

Methods: The brains of 25 cases of pathologically confirmed PSP were evaluated with immunohistochemistry for α-synuclein and tau. Multiple immunofluorescent stains were applied to analyze the expression of tau and α-synuclein aggregates in catecholaminergic neurons. Patients' clinical symptoms were retrospectively recorded.

Results: Deposits α-synuclein in the form of typical Lewy bodies (LBs) were only found in two PSP cases (8%) that fulfilled the clinical subtype of PSP known as Richardson's syndrome (RS). LBs were present in the locus ceruleus (LC), substantia nigra pars compacta (SNc), basal forebrain, amygdala and cingulated cortex in a distribution mimicking that of Parkinson's disease (PD). Triple-immunolabeling revealed co-expression of α-synuclein and tau proteins in some tyrosine hydroxilase (TH)-positive neurons of the LC and SNc.

Conclusions: There is no apparent clinical correlation between the presence of LBs in PSP. Tau protein co-aggregate with α-synuclein in catecholaminergic neurons of PSP brains suggesting a synergistic interaction between the two proteins. This is in keeping with the current view of neurodegenerative disorders as "misfolded protein diseases".

No MeSH data available.


Related in: MedlinePlus

Coronal section through the ventral mesencephalon showing the obtained dual stain for α-synuclein (TH; brown) and tau (red). At the level of the substantia nigra pars compacta (SNc), up to three different types of melanin-containing neurons were observed, comprising (i) brown-stained neurons containing Lewy bodies (LBs; arrows), (ii) red-stained neurons with tau immunoreactivity (arrowheads); and (iii) neurons showing both LBs and tau deposits (asterisks). Scale bar is 4,000 μm in (A); 200 μm in (B) and 50 μm in the high-magnification insets shown in panels (C) and (D).
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Figure 1: Coronal section through the ventral mesencephalon showing the obtained dual stain for α-synuclein (TH; brown) and tau (red). At the level of the substantia nigra pars compacta (SNc), up to three different types of melanin-containing neurons were observed, comprising (i) brown-stained neurons containing Lewy bodies (LBs; arrows), (ii) red-stained neurons with tau immunoreactivity (arrowheads); and (iii) neurons showing both LBs and tau deposits (asterisks). Scale bar is 4,000 μm in (A); 200 μm in (B) and 50 μm in the high-magnification insets shown in panels (C) and (D).

Mentions: When considering catecholaminergic nuclei such as the SNc and the LC, the dual colorimetric detection of tau and α-synuclein showed different types of neuromelanin-containing neurons, comprising (i) neurons with tau deposits; (ii) neurons with LBs (quite often with more than one LB); and (iii) neurons with both types of aggregates, i.e., tau and LBs (Figures 1, 2). These three types of neurons were also observed in the conducted triple immunofluorescent stains, which also fully confirmed the monoaminergic nature of these neurons by showing that all these types of neurons were also positive for TH, both at the level of the SNc and the LC (Figure 3). Furthermore, it is also worth noting that a minimal number of TH+ neurons completely lacked any type of protein aggregates (Figure 3).


Midbrain catecholaminergic neurons co-express α-synuclein and tau in progressive supranuclear palsy.

Erro Aguirre ME, Zelaya MV, Sánchez Ruiz de Gordoa J, Tuñón MT, Lanciego JL - Front Neuroanat (2015)

Coronal section through the ventral mesencephalon showing the obtained dual stain for α-synuclein (TH; brown) and tau (red). At the level of the substantia nigra pars compacta (SNc), up to three different types of melanin-containing neurons were observed, comprising (i) brown-stained neurons containing Lewy bodies (LBs; arrows), (ii) red-stained neurons with tau immunoreactivity (arrowheads); and (iii) neurons showing both LBs and tau deposits (asterisks). Scale bar is 4,000 μm in (A); 200 μm in (B) and 50 μm in the high-magnification insets shown in panels (C) and (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356077&req=5

Figure 1: Coronal section through the ventral mesencephalon showing the obtained dual stain for α-synuclein (TH; brown) and tau (red). At the level of the substantia nigra pars compacta (SNc), up to three different types of melanin-containing neurons were observed, comprising (i) brown-stained neurons containing Lewy bodies (LBs; arrows), (ii) red-stained neurons with tau immunoreactivity (arrowheads); and (iii) neurons showing both LBs and tau deposits (asterisks). Scale bar is 4,000 μm in (A); 200 μm in (B) and 50 μm in the high-magnification insets shown in panels (C) and (D).
Mentions: When considering catecholaminergic nuclei such as the SNc and the LC, the dual colorimetric detection of tau and α-synuclein showed different types of neuromelanin-containing neurons, comprising (i) neurons with tau deposits; (ii) neurons with LBs (quite often with more than one LB); and (iii) neurons with both types of aggregates, i.e., tau and LBs (Figures 1, 2). These three types of neurons were also observed in the conducted triple immunofluorescent stains, which also fully confirmed the monoaminergic nature of these neurons by showing that all these types of neurons were also positive for TH, both at the level of the SNc and the LC (Figure 3). Furthermore, it is also worth noting that a minimal number of TH+ neurons completely lacked any type of protein aggregates (Figure 3).

Bottom Line: Deposits α-synuclein in the form of typical Lewy bodies (LBs) were only found in two PSP cases (8%) that fulfilled the clinical subtype of PSP known as Richardson's syndrome (RS).Tau protein co-aggregate with α-synuclein in catecholaminergic neurons of PSP brains suggesting a synergistic interaction between the two proteins.This is in keeping with the current view of neurodegenerative disorders as "misfolded protein diseases".

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Complejo Hospitalario de Navarra Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IDISNA) Pamplona, Spain.

ABSTRACT

Objective: To analyze the frequency and distribution of α-synuclein deposits in progressive supranuclear palsy (PSP).

Methods: The brains of 25 cases of pathologically confirmed PSP were evaluated with immunohistochemistry for α-synuclein and tau. Multiple immunofluorescent stains were applied to analyze the expression of tau and α-synuclein aggregates in catecholaminergic neurons. Patients' clinical symptoms were retrospectively recorded.

Results: Deposits α-synuclein in the form of typical Lewy bodies (LBs) were only found in two PSP cases (8%) that fulfilled the clinical subtype of PSP known as Richardson's syndrome (RS). LBs were present in the locus ceruleus (LC), substantia nigra pars compacta (SNc), basal forebrain, amygdala and cingulated cortex in a distribution mimicking that of Parkinson's disease (PD). Triple-immunolabeling revealed co-expression of α-synuclein and tau proteins in some tyrosine hydroxilase (TH)-positive neurons of the LC and SNc.

Conclusions: There is no apparent clinical correlation between the presence of LBs in PSP. Tau protein co-aggregate with α-synuclein in catecholaminergic neurons of PSP brains suggesting a synergistic interaction between the two proteins. This is in keeping with the current view of neurodegenerative disorders as "misfolded protein diseases".

No MeSH data available.


Related in: MedlinePlus