Abstract
Parkinson’s disease (PD) and multiple system atrophy are types of adult-onset neurodegenerative disorders named synucleinopathies, which are characterized by prominent intracellular α-synuclein (αSyn) aggregates. We have previously found that αSyn aggregates and the vulnerability of dopaminergic neurons in the mouse brain are partly associated with the expression of fatty acid-binding protein 3 (FABP3, heart FABP). However, it remains to be elucidated whether FABP3 accumulation is associated with αSyn aggregates in human tissues. Here, we histologically studied FABP3 expression in human tissues obtained from patients with synucleinopathies, patients with Alzheimer disease (AD) and controls. We found that (1) a variety of neurons expressed the FABP3 protein in human brain tissues, (2) FABP3 was colocalized with αSyn aggregates in the brains of individuals with synucleinopathies but not with amyloid β or p-tau aggregates in the brains of individuals with AD, and (3) FABP3 was not present in p-αSyn deposits in biopsied skin tissues from individuals with PD. These findings suggest that FABP3 expression is associated with αSyn aggregation in synucleinopathies and provide new insights into the involvement of FABP3 in synucleinopathies.
Highlights
Parkinson’s disease (PD) is a secondary common neurodegenerative disorder affecting >1% of the population over 65 years of age worldwide (de Lau and Breteler, 2006)
In a previous study on model mice with PD induced by 1-methyl1,2,3,6-tetrahydropyridine (MPTP), we found that αSyn binds to FABP3 and that αSyn aggregates with FABP3 accumulation are abundant in damaged DA neurons (Shioda et al, 2014)
FABP3-ir proteins were expressed in melanin-positive DA neurons in the substantia nigra (SN) (Figure 1A), in melanin-positive locus coeruleus neurons in the pons (Figure 1B), in oculomotor neurons in the midbrain (Figure 1C) and cortical neurons in the entorhinal cortex (EC) (Figure 1D) in autopsied brain tissues from CNs
Summary
Parkinson’s disease (PD) is a secondary common neurodegenerative disorder affecting >1% of the population over 65 years of age worldwide (de Lau and Breteler, 2006). The histopathological features of PD include loss of dopaminergic (DA) neurons in the substantia nigra (SN) and the presence of cytoplasmic protein aggregates, known as Lewy bodies (LBs) (Gibb and Lees, 1988). PD and dementia with LBs (DLB) are designated as synucleinopathies, which are neurodegenerative disorders characterized by prominent intracellular αSyn aggregates (McCann et al, 2014). Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that is clinically characterized by a combination of poorly levodopa (L-dopa)-responsive parkinsonism, cerebellar dysfunction and autonomic failure (Yabe et al, 2006). The histopathological features of MSA include the presence of glial and neuronal protein aggregates, known as glial cytoplasmic inclusions (GCIs) and neuronal cytoplasmic inclusions (NCIs), respectively (Wakabayashi et al, 1998; Wakabayashi and Takahashi, 2006; Homma et al, 2016). The molecular mechanisms of αSyn aggregation remain to be elucidated
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