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

Marã­A Elena Erro Aguirre,Marã­A Teresa Tuã±Ã³N,Josã© Luis Lanciego,Javier Sã¡Nchez Ruiz De Gordoa,Marã­A Victoria Zelaya

doi:10.3389/fnana.2015.00025

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”.

Highlights

Aggregation of α-synuclein in the form of Lewy bodies (LBs) is the histopathological hallmark of idiopathic Parkinson’s disease (PD) and dementia with LBs (DLB; Spillantini et al, 1997)
Clinical Features of the progressive supranuclear palsy (PSP) Patients The first patient was an 84-year-old woman who underwent consultation at the Neurology Department complaining of progressive gait unsteadiness, with postural imbalance and frequent falls reported over the previous year
Ocular motility was normal, generalized bradykinesia and rigidity were present with a rigid neck extension posture, deep tendon reflexes were brisk, gait was slow and unsteady with severe impairment of postural righting reflexes

Summary

Introduction

Aggregation of α-synuclein in the form of Lewy bodies (LBs) is the histopathological hallmark of idiopathic Parkinson’s disease (PD) and dementia with LBs (DLB; Spillantini et al, 1997). LBs are present in the 50% of Alzheimer’s disease brains (AD; Hamilton, 2000) but they are less frequently found in other neurodegenerative diseases such as progressive supranuclear palsy (PSP; Abhinav et al, 2011). At present it is well known that protein aggregation phenomena represent a crucial pathobiological mechanism shared by neurodegenerative diseases such AD, PD, PSP and Huntington disease. These diseases have often been categorized as ‘‘misfolded protein diseases’’, since cross-seeding of misfolded proteins. The pathology of PSP is characterized by the accumulation of abnormal tau protein within neurons (neurofibrillary tangles) and glial cells (tufted astrocytes and coiled bodies) in the brain. Whether the presence of LBs in PSP represents a normal aging process or the coexistence with PD remains unclear (Uchikado et al, 2006)

Methods

Results

Conclusion