Fatty Acid-Binding Protein 3 Expression in the Brain and Skin in Human Synucleinopathies

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.

Keywords: Parkinson’s disease; fatty acid-binding protein; human; multiple system atrophy; α-synuclein.

FIGURE 1

Immunohistochemical analysis of FABP3 protein expression in autopsied brain tissues of CNs. We used fluorescence microscopy to show FABP3 expression and optical microscopy to identify melanin-positive DA neurons and locus coeruleus (LC) neurons. The nuclei of neurons were identified morphologically by DAPI (blue) staining. IF staining of FABP3 (red) and melanin (black) in DA neurons in the SN of CNs is shown in high-magnification images (A). IF staining of FABP3 (red) and melanin (black) in LC neurons in the pons of CNs is shown in high-magnification images (B). IF staining of FABP3 (red) in the oculomotor neurons (ON) of CNs is shown in high-magnification images (C). IF staining of FABP3 (red) in the cortical neurons (CoN) in the EC of CNs is shown in high-magnification images (D). FABP3-ir proteins in melanin-positive neurons were expressed mostly in the cytoplasm. FABP3-ir proteins were also expressed in oculomotor neurons and cortical neurons other than melanin-positive neurons. Scale bars = 50 μm.

FIGURE 2

Correlation between FABP3 protein accumulation and αSyn aggregation in synucleinopathies. IF staining of FABP3 (red) and p-αSyn (green) in the SN in MSA tissue is shown in low-magnification (A) and high-magnification (B) images; staining in the SN in PD tissue is shown in low-magnification images (C); and staining in the SN in CN tissue is shown in high-magnification images (D). (A–C) shows that FABP3 was colocalized with p-αSyn aggregates in synucleinopathies. In contrast, (D) shows that p-αSyn aggregates were not observed in the SN in CNs, although FABP3 protein was detected in DA neurons. The ratio of FABP3 protein accumulations to p-αSyn aggregates in the striatum in MSA tissue and in the EC in PD tissue was quantitatively analyzed (E) (p = 0.666). (E) shows that FABP3 accumulations were colocalized with most p-αSyn aggregates in both PD and MSA tissues. IF staining of FABP3 (red) and αSyn fibrils (green) in the SN in MSA tissue is shown in low-magnification (F) and high-magnification (G) images; staining in the SN in PD tissue is shown in low-magnification images (H); and staining in the SN in CN tissue is shown in high-magnification images (I). (F–H) shows that FABP3 accumulations were colocalized with αSyn fibrils in synucleinopathies. In contrast, (I) shows that αSyn fibrils were not observed in the SN in CNs, although FABP3 protein was detected in DA neurons. The ratio of FABP3 protein accumulations to αSyn fibrils in the striatum in MSA tissue and in the EC in PD tissue was quantitatively analyzed (J) (p = 0.119). (J) shows that FABP3 accumulations were colocalized with approximately 80% of αSyn fibrils in both PD and MSA tissues. Scale bars = 20 μm.

FIGURE 3

No FABP3 protein expression in AD pathologyIF staining of FABP3 (red) and p-tau aggregates (green) in the frontal cortex in AD tissue (A). IF staining of FABP3 (red) and amyloid β aggregates (green) in the frontal cortex in AD tissue (B). FABP3 accumulation was not observed in amyloid β aggregates (A) or p-tau aggregates (B) in AD tissue. Nuclear staining with hematoxylin showed that p-tau-positive aggregates were NFTs (C). Scale bars = 50 μm.

FIGURE 4

No correlation between p-αSyn deposits and FABP3 accumulation in biopsied skin tissues of patients with PD. IF staining of p-αSyn (red) and FABP3 (green) in biopsied skin tissues of patients with PD. The nuclei were identified by DAPI (blue) staining. Weak FABP3 protein expression was observed in the cytoplasm of dermal sweat duct cells of patients with PD. On the other hand, p-αSyn deposits were observed in the dermal cells (arrows) of patients with PD. FABP3 accumulation was not observed in dermal p-αSyn deposits in PD tissues. Scale bars = 50 μm.