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Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL
Anderson AJ, Stoltzner S, Lai F, Su J, Nixon RA.. Neurobiology of aging, 2000-07-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
We have previously shown that Alzheimer disease (AD) brain exhibits terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) for DNA damage and morphological evidence for apoptosis. Down syndrome (DS) is a neurodegenerative disorder that exhibits significant neuropathological parallels with AD. In accordance with these parallels and the need to clarify the mechanism of cell death in DS and AD, we investigated two principal issues in the present study. First, we investigated the hypothesis that TUNEL labeling for DNA damage and morphological evidence for apoptosis is also present in the DS brain. All DS cases employed had a neuropathological diagnosis of AD. Analysis of these cases showed that DS brain exhibits a significant increase in the number of TUNEL-labeled nuclei relative to controls matched for age, Postmortem Delay, and Archival Length, and that a subset of TUNEL-positive nuclei exhibits apoptotic morphologies. We also report that Archival Length in 10% formalin can significantly affect TUNEL labeling in postmortem human brain, and therefore, that Archival Length must be controlled for as a variable in this type of study. Second, we investigated whether biochemical evidence for the mechanism of cell death in DS and AD could be detected. To address this question we employed pulsed-field gel electrophoresis (PFGE) as a sensitive method to evaluate DNA integrity. Although apoptotic oligonucleosomal laddering has not previously been observed in AD, PFGE of DNA from control, DS and AD brain in the present study revealed evidence of high molecular weight DNA fragmentation indicative of apoptosis. This represents biochemical support for an apoptotic mechanism of cell death in DS and AD.
What this study adds
Evidence grade: Low
Brain tissue from people with Down syndrome and Alzheimer's disease showed increased TUNEL labeling for DNA damage and some apoptotic morphologies compared with controls. This is a post-mortem tissue study of cell death mechanisms and does not test any treatment.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Anderson, A. J., Stoltzner, S., Lai, F., Su, J., & Nixon, R. A. (2000). Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL. Neurobiology of aging. https://doi.org/10.1016/s0197-4580(00)00126-3
Vancouver
Anderson AJ, Stoltzner S, Lai F, Su J, Nixon RA. Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL. Neurobiology of aging. 2000. doi:10.1016/s0197-4580(00)00126-3. PMID: 10924764.
BibTeX
@article{anderson2000-10924764,
author = {Anderson, A. J. and Stoltzner, S. and Lai, F. and Su, J. and Nixon, R. A.},
title = {{Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL}},
journal = {Neurobiology of aging},
year = {2000},
doi = {10.1016/s0197-4580(00)00126-3},
pmid = {10924764},
url = {https://doi.org/10.1016/s0197-4580(00)00126-3}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- We have previously shown that Alzheimer disease (AD) brain exhibits terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) for DNA damage and morphological evidence for apoptosis.
- Down syndrome (DS) is a neurodegenerative disorder that exhibits significant neuropathological parallels with AD.
- Analysis of these cases showed that DS brain exhibits a significant increase in the number of TUNEL-labeled nuclei relative to controls matched for age, Postmortem Delay, and Archival Length, and that a subset of TUNEL-positive nuclei exhibits apoptotic morphologies.
- We also report that Archival Length in 10% formalin can significantly affect TUNEL labeling in postmortem human brain, and therefore, that Archival Length must be controlled for as a variable in this type of study.
- Although apoptotic oligonucleosomal laddering has not previously been observed in AD, PFGE of DNA from control, DS and AD brain in the present study revealed evidence of high molecular weight DNA fragmentation indicative of apoptosis.
Why it matters
Brain tissue from people with Down syndrome and Alzheimer's disease showed increased TUNEL labeling for DNA damage and some apoptotic morphologies compared with controls. This is a post-mortem tissue study of cell death mechanisms and does not test any treatment.
Study details
- Evidence strengthLow
How this study scored 44/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (OpenAlex, 2026-10-29) |
| 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 | 2000 — older than 20 years, still counted |
| 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 | 4 / 7 | Cited 87 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.1 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 4 / 6 | Cited 8.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Ralph A. Nixon: h-index 115 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10924764) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
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