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Highly pathogenic Alzheimer's disease presenilin 1 P117R mutation causes a specific increase in p53 and p21 protein levels and cell cycle dysregulation in human lymphocytes
Bialopiotrowicz E, Szybinska A, Kuzniewska B, Buizza L, Uberti D, Kuznicki J, Wojda U.. Journal of Alzheimer's disease : JAD, 2012-01-01
Topic: Amyloid, tau and blood-test diagnosis
Cell cycle (CC) reentry in neurons precedes the formation of amyloid-β (Aβ) plaques in Alzheimer's disease (AD). CC alterations were also detected in lymphocytes from sporadic AD patients. In the present study, we investigated the influence of nine presenilin 1 (PS1) mutations (P117R, M139V, L153V, H163R, S170F, F177L, I213F, L226F, E318G) on CC and Aβ production in immortalized B-lymphocytes from familial AD (FAD) patients and in stably transfected human embryonic kidney cells. In both cell types, only the P117R mutation increased levels of key G1/S phase regulatory proteins, p53, and its effector p21, causing G1 phase prolongation with simultaneous S phase shortening, and lowering basal apoptosis. The CC changes were rescued by inhibition of p53, but not of γ-secretase. Moreover, the investigated PS1 mutants showed differences in the increased levels of secreted Aβ40 and Aβ42 and in Aβ42/Aβ40 ratios, but these differences did not correlate with CC patterns. Altogether, we found that both CC regulation and Aβ production differentiate PS1 mutations, and that CC PS1 activity is mediated by p53/p21 signaling but not by γ-secretase activity. The identified CC dysregulation linked with increased p53 and p21 protein levels distinguishes the highly pathogenic PS1 P117R mutation and may contribute to the specific severity of the clinical progression of FAD associated with the mutation in the PS1 117 site. These findings suggest that impairment in lymphocyte CC might play a pathogenic function in AD and are relevant to the development of new diagnostic approaches and personalized therapeutic strategies.
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APA 7th
Bialopiotrowicz, E., Szybinska, A., Kuzniewska, B., Buizza, L., Uberti, D., Kuznicki, J., et al. (2012). Highly pathogenic Alzheimer's disease presenilin 1 P117R mutation causes a specific increase in p53 and p21 protein levels and cell cycle dysregulation in human lymphocytes. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-2012-121129
Vancouver
Bialopiotrowicz E, Szybinska A, Kuzniewska B, Buizza L, Uberti D, Kuznicki J, et al. Highly pathogenic Alzheimer's disease presenilin 1 P117R mutation causes a specific increase in p53 and p21 protein levels and cell cycle dysregulation in human lymphocytes. Journal of Alzheimer's disease : JAD. 2012. doi:10.3233/jad-2012-121129. PMID: 22810102.
BibTeX
@article{bialopiotrowicz2012-22810102,
author = {Bialopiotrowicz, E. and Szybinska, A. and Kuzniewska, B. and Buizza, L. and Uberti, D. and Kuznicki, J. and Wojda, U.},
title = {{Highly pathogenic Alzheimer's disease presenilin 1 P117R mutation causes a specific increase in p53 and p21 protein levels and cell cycle dysregulation in human lymphocytes}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2012},
doi = {10.3233/jad-2012-121129},
pmid = {22810102},
url = {https://doi.org/10.3233/jad-2012-121129}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Altogether, we found that both CC regulation and Aβ production differentiate PS1 mutations, and that CC PS1 activity is mediated by p53/p21 signaling but not by γ-secretase activity.
- The identified CC dysregulation linked with increased p53 and p21 protein levels distinguishes the highly pathogenic PS1 P117R mutation and may contribute to the specific severity of the clinical progression of FAD associated with the mutation in the PS1 117 site.
- These findings suggest that impairment in lymphocyte CC might play a pathogenic function in AD and are relevant to the development of new diagnostic approaches and personalized therapeutic strategies.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22810102) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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