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. 2022 Apr 25:14:793353.
doi: 10.3389/fnagi.2022.793353. eCollection 2022.

Expression Pattern of p62 in Primary Age-Related Tauopathy: Staging of p62 in PART

Xin Wang  1   2 , Lei Zhang  1   2 , Hui Lu  1 , Juanli Wu  1 , Huazheng Liang  3 , Bing Sun  1 , Keqing Zhu  1   2
Affiliations

Expression Pattern of p62 in Primary Age-Related Tauopathy: Staging of p62 in PART

Xin Wang et al. Front Aging Neurosci. .

Abstract

The present study analyzed the distribution pattern of p62 immunoreactivity in brains of primary age-related tauopathy (PART) and Braak NFT matched pre-AD and Alzheimer's disease (AD) patients using immunohistochemistry in combination with semi-quantitative evaluation. In PART and AD brains, p62 was found positive in seven regions, including the neocortex, thalamus, basal ganglia, hippocampus, brainstem, cerebellar dentate nucleus, and the cervical spinal cord. There was a positive correlation between the Braak NFT stage and the distribution of p62 expression. Six stages of expression of p62 were proposed from the present study. Expression of p62 in the hippocampus of PART and AD was classified stage I, the brainstem stage II, the thalamus stage I _I _I, the basal ganglia stage IV, the neocortex stage V, the cerebellum and the cervical spinal cord stage VI. The hippocampus was the site initially affected by p62, especially the CA1 and the subiculum. They might be the earliest accumulation site of p62.

Keywords: Alzheimier’s disease; Braak NFT stage; hippocampus; p62; primary age-related tauopathy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Immunohistochemistry of the p62 + in PART brain area. (A) Gyrus pre/postcentralis, (B) Hypothalamus, (C) Caudatum/Putamen, (D) Amygdala, (E) Colliculus inferior/pons, (F) Cerebellum, (G) Spinal cord cervical, (H) Granule cell layer of hippocampus dentate gyrus (DG), (I) CA4, (J) CA1, (K) Subiculum (Sub), (L) Entorhinal Cortex(EC). Arrow point positive cell. Scale bars, (A–G) 20 μm, (H–L) 100 μm.
FIGURE 2
FIGURE 2
(A) Quantification of the positive rate of p62 cell in PART and AD. Values represent mean ± SEM (n = 9–16 subjects; **p < 0.01; Kruskal–Wallis H test). (B) Quantification of the positive rate of p62 + cell in PART. Values represent mean ± SEM (n = 5–9 subjects; Kruskal–Wallis H test). (C) Quantification of the positive rate of p62 + cell in PART in brain areas. Values represent mean ± SEM (n = 0–9; *p < 0.05; Kruskal–Wallis H test). (D) Quantification of the positive rate of p62 + cell in PART in brain areas. Values represent mean ± SEM (n = 0–9; **p < 0.01; Kruskal-Wallis H test). (E) Quantification of the positive rate of p62 + cell in AD in brain areas. Values represent mean ± SEM (n = 0–9; *p < 0.05; Kruskal–Wallis H test). (F) Quantification of the positive rate of p62 + cell in AD braak stage III-IV in brain areas. Values represent mean ± SEM (n = 8–18; *p < 0.05; Kruskal–Wallis H test). (G) Quantification of the positive rate of p62 + cell in hippocampus. Values represent mean ± SEM (n = 8–18; **p < 0.01; Mann–Whitney U test).
FIGURE 3
FIGURE 3
The schematic about the location of the tissues required for p62 staining. (A) Lateral view of brain, all lobes. (B) Sagittal cut of brain. (C) Coronal cut at basal ganglia. (D) Coronal cut of brain at hippocampus. Granule cell layer of dentate gyrus (DG), Subiculum (Sub), Entorhinal Cortex (EC).
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