Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2022
Author(s)
Felipe Salech
Carol D. SanMartín
Jorge Concha-Cerda
Esteban Romero-Hernández
Daniela P. Ponce
Gianella Liabeuf
Nicole K. Rogers
Paola Murgas
Bárbara Bruna
Jamileth More
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85137125834
WoS ID
WOS:000845805300001
DOI
URL
URL Institutional Repository
Abstract
<jats:p>Recent studies suggest that cellular senescence plays a role in Alzheimer’s Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-β-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients.</jats:p>
Subjects
aging

; 

alzheimer’s disease

; 

amci

; 

cellular senescence

; 

peripheral blood mononuclear cells

; 

alzheimer disease

; 

biomarkers

; 

cellular senescence

; 

cognitive dysfunction

; 

humans

; 

interleukin-6

; 

leukocytes, mononuclear

; 

rna, messenger

; 

tumor suppressor protein p53

; 

beta galactosidase

; 

cell marker

; 

dna

; 

histone h2a

; 

interleukin 6

; 

interleukin 8

; 

lipofuscin

; 

messenger rna

; 

protein p16

; 

protein p53

; 

biological marker

; 

interleukin 6

; 

messenger rna

; 

protein p53

; 

aged

; 

alzheimer disease

; 

article

; 

brain tissue

; 

cell aging

; 

clinical article

; 

controlled study

; 

diabetes mellitus

; 

dna damage response

; 

enzyme activity

; 

enzyme linked immunosorbent assay

; 

female

; 

flow cytometry

; 

frontal cortex

; 

g1 phase cell cycle checkpoint

; 

hippocampal tissue

; 

hippocampus

; 

histone phosphorylation

; 

human

; 

human cell

; 

human tissue

; 

hypercholesterolemia

; 

hypertension

; 

immunocytochemistry

; 

immunofluorescence assay

; 

insulin resistance

; 

male

; 

messenger rna synthesis

; 

mild cognitive impairment

; 

molecular pathology

; 

montreal cognitive assessment

; 

mrna expression level

; 

pathophysiology

; 

peripheral blood mononuclear cell

; 

real time polymerase chain reaction

; 

senescence-associated secretory phenotype

; 

alzheimer disease

; 

cell aging

; 

cognitive defect

; 

genetics

; 

metabolism

; 

mononuclear cell

; 

pathology