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Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model
Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS.. Proceedings of the National Academy of Sciences of the United States of America, 2010-10-11
Topic: Disease mechanisms in lab and animal studies
Synaptic dysfunction and the loss of synapses are early pathological features of Alzheimer's disease (AD). Synapses are sites of high energy demand and extensive calcium fluctuations; accordingly, synaptic transmission requires high levels of ATP and constant calcium fluctuation. Thus, synaptic mitochondria are vital for maintenance of synaptic function and transmission through normal mitochondrial energy metabolism, distribution and trafficking, and through synaptic calcium modulation. To date, there has been no extensive analysis of alterations in synaptic mitochondria associated with amyloid pathology in an amyloid β (Aβ)-rich milieu. Here, we identified differences in mitochondrial properties and function of synaptic vs. nonsynaptic mitochondrial populations in the transgenic mouse brain, which overexpresses the human mutant form of amyloid precursor protein and Aβ. Compared with nonsynaptic mitochondria, synaptic mitochondria showed a greater degree of age-dependent accumulation of Aβ and mitochondrial alterations. The synaptic mitochondrial pool of Aβ was detected at an age as young as 4 mo, well before the onset of nonsynaptic mitochondrial and extensive extracellular Aβ accumulation. Aβ-insulted synaptic mitochondria revealed early deficits in mitochondrial function, as shown by increased mitochondrial permeability transition, decline in both respiratory function and activity of cytochrome c oxidase, and increased mitochondrial oxidative stress. Furthermore, a low concentration of Aβ (200 nM) significantly interfered with mitochondrial distribution and trafficking in axons. These results demonstrate that synaptic mitochondria, especially Aβ-rich synaptic mitochondria, are more susceptible to Aβ-induced damage, highlighting the central importance of synaptic mitochondrial dysfunction relevant to the development of synaptic degeneration in AD.
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APA 7th
Du, H., Guo, L., Yan, S., Sosunov, A. A., McKhann, G. M., & Yan, S. S. (2010). Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1006586107
Vancouver
Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS. Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proceedings of the National Academy of Sciences of the United States of America. 2010. doi:10.1073/pnas.1006586107. PMID: 20937894.
BibTeX
@article{du2010-20937894,
author = {Du, H. and Guo, L. and Yan, S. and Sosunov, A. A. and McKhann, G. M. and Yan, S. S.},
title = {{Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2010},
doi = {10.1073/pnas.1006586107},
pmid = {20937894},
url = {https://doi.org/10.1073/pnas.1006586107}
}
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Key findings
- To date, there has been no extensive analysis of alterations in synaptic mitochondria associated with amyloid pathology in an amyloid β (Aβ)-rich milieu.
- Compared with nonsynaptic mitochondria, synaptic mitochondria showed a greater degree of age-dependent accumulation of Aβ and mitochondrial alterations.
- Aβ-insulted synaptic mitochondria revealed early deficits in mitochondrial function, as shown by increased mitochondrial permeability transition, decline in both respiratory function and activity of cytochrome c oxidase, and increased mitochondrial oxidative stress.
- Furthermore, a low concentration of Aβ (200 nM) significantly interfered with mitochondrial distribution and trafficking in axons.
- These results demonstrate that synaptic mitochondria, especially Aβ-rich synaptic mitochondria, are more susceptible to Aβ-induced damage, highlighting the central importance of synaptic mitochondrial dysfunction relevant to the development of synaptic degeneration in AD.
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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 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 (Proceedings of the National Academy of Sciences of the United States of America) |
| 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 | 2010 — 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 | Laboratory or animal study (title names “mouse”) — scores zero |
| 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 20937894) |
| 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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