AUTHOR=Dong Wei , Cui Meng-Chao , Hu Wen-Zheng , Zeng Qi , Wang Yi-Long , Zhang Wei , Huang Yue 

TITLE=Genetic and Molecular Evaluation of SQSTM1/p62 on the Neuropathologies of Alzheimer’s Disease

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.829232

DOI=10.3389/fnagi.2022.829232

ISSN=1663-4365

ABSTRACT=<p>Sequestosome 1 (<italic>SQSTM1</italic>)/p62 is a multifunctional scaffolding protein and plays a major role in the cellular processes of autophagy, upregulation of which has been shown in several neurodegenerative disorders, including Alzheimer’s disease (AD). To investigate its genetic effects and relationship with AD pathologies, we analyzed the genetic associations of <italic>SQSTM1</italic> rs4935 with the risk of AD and the levels of AD biomarkers using the AD Neuroimaging Initiative (ADNI) Database. We further analyzed the distribution pattern of p62 immunoreactivity in relation to AD pathologies in the postmortem human brain tissues from AD and non-AD controls. We found that <italic>SQSTM1</italic> rs4935 was not associated with the risk of AD, but its T allele was significantly associated with decreased β-amyloid (1–42) (Aβ<sub>42</sub>) levels in the cerebral spinal fluid (CSF) of patients with AD (β = −9.336, <italic>p</italic> = 0.022). In addition, p62 immunoreactivity in AD is increased, but it shows an inverse relationship to Aβ deposition. A small proportion of senile plaques show p62 positive neurites. Our results suggest that <italic>SQSTM1</italic>/p62 may play an important role in the progression of AD <italic>via</italic> associations with Aβ<sub>42</sub> levels in CSF and Aβ deposition in the brain of patients with AD.</p>