Genetic and Molecular Evaluation of SQSTM1/p62 on the Neuropathologies of Alzheimer's Disease
Copyright © 2022 Dong, Cui, Hu, Zeng, Wang, Zhang and Huang..
Sequestosome 1 (SQSTM1)/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 SQSTM1 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 SQSTM1 rs4935 was not associated with the risk of AD, but its T allele was significantly associated with decreased β-amyloid (1-42) (Aβ42) levels in the cerebral spinal fluid (CSF) of patients with AD (β = -9.336, p = 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 SQSTM1/p62 may play an important role in the progression of AD via associations with Aβ42 levels in CSF and Aβ deposition in the brain of patients with AD.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Frontiers in aging neuroscience - 14(2022) vom: 15., Seite 829232 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dong, Wei [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Alzheimer’s disease |
|---|
| Anmerkungen: |
Date Revised 19.03.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3389/fnagi.2022.829232 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM338266895 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM338266895 | ||
| 003 | DE-627 | ||
| 005 | 20231226000304.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fnagi.2022.829232 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1127.xml |
| 035 | |a (DE-627)NLM338266895 | ||
| 035 | |a (NLM)35296031 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dong, Wei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic and Molecular Evaluation of SQSTM1/p62 on the Neuropathologies of Alzheimer's Disease |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 19.03.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2022 Dong, Cui, Hu, Zeng, Wang, Zhang and Huang. | ||
| 520 | |a Sequestosome 1 (SQSTM1)/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 SQSTM1 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 SQSTM1 rs4935 was not associated with the risk of AD, but its T allele was significantly associated with decreased β-amyloid (1-42) (Aβ42) levels in the cerebral spinal fluid (CSF) of patients with AD (β = -9.336, p = 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 SQSTM1/p62 may play an important role in the progression of AD via associations with Aβ42 levels in CSF and Aβ deposition in the brain of patients with AD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a SQSTM1/p62 | |
| 650 | 4 | |a biomarkers | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a neuropathology | |
| 700 | 1 | |a Cui, Meng-Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Wen-Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yi-Long |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yue |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in aging neuroscience |d 2009 |g 14(2022) vom: 15., Seite 829232 |w (DE-627)NLM198856024 |x 1663-4365 |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2022 |g day:15 |g pages:829232 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fnagi.2022.829232 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2022 |b 15 |h 829232 | ||