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Bioenergetic mechanisms in astrocytes may contribute to amyloid plaque deposition and toxicity
Fu W, Shi D, Westaway D, Jhamandas JH.. The Journal of biological chemistry, 2015-03-26
Topic: Brain proteins, microglia and lab models
Plain-language summary
Alzheimer disease (AD) is characterized neuropathologically by synaptic disruption, neuronal loss, and deposition of amyloid β (Aβ) protein in brain structures that are critical for memory and cognition. There is increasing appreciation, however, that astrocytes, which are the major non-neuronal glial cells, may play an important role in AD pathogenesis. Unlike neurons, astrocytes are resistant to Aβ cytotoxicity, which may, in part, be related to their greater reliance on glycolytic metabolism. Here we show that, in cultures of human fetal astrocytes, pharmacological inhibition or molecular down-regulation of a main enzymatic regulator of glycolysis, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB3), results in increased accumulation of Aβ within and around astrocytes and greater vulnerability of these cells to Aβ toxicity. We further investigated age-dependent changes in PFKFB3 and astrocytes in AD transgenic mice (TgCRND8) that overexpress human Aβ. Using a combination of Western blotting and immunohistochemistry, we identified an increase in glial fibrillary acidic protein expression in astrocytes that paralleled the escalation of the Aβ plaque burden in TgCRND8 mice in an age-dependent manner. Furthermore, PFKFB3 expression also demonstrated an increase in these mice, although at a later age (9 months) than GFAP and Aβ. Immunohistochemical staining showed significant reactive astrogliosis surrounding Aβ plaques with increased PFKFB3 activity in 12-month-old TgCRND8 mice, an age when AD pathology and behavioral deficits are fully manifested. These studies shed light on the unique bioenergetic mechanisms within astrocytes that may contribute to the development of AD pathology.
What this study adds
Evidence grade: Low
In cultures of human fetal astrocytes and in Alzheimer's disease transgenic mice, inhibiting or reducing PFKFB3 increased accumulation of amyloid β within and around astrocytes and made these cells more vulnerable to amyloid β toxicity. It is a laboratory and animal study and does not test any treatment, cure or prevention in people.
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
Fu, W., Shi, D., Westaway, D., & Jhamandas, J. H. (2015). Bioenergetic mechanisms in astrocytes may contribute to amyloid plaque deposition and toxicity. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m114.618157
Vancouver
Fu W, Shi D, Westaway D, Jhamandas JH. Bioenergetic mechanisms in astrocytes may contribute to amyloid plaque deposition and toxicity. The Journal of biological chemistry. 2015. doi:10.1074/jbc.m114.618157. PMID: 25814669.
BibTeX
@article{fu2015-25814669,
author = {Fu, W. and Shi, D. and Westaway, D. and Jhamandas, J. H.},
title = {{Bioenergetic mechanisms in astrocytes may contribute to amyloid plaque deposition and toxicity}},
journal = {The Journal of biological chemistry},
year = {2015},
doi = {10.1074/jbc.m114.618157},
pmid = {25814669},
url = {https://doi.org/10.1074/jbc.m114.618157}
}
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
- Here we show that, in cultures of human fetal astrocytes, pharmacological inhibition or molecular down-regulation of a main enzymatic regulator of glycolysis, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB3), results in increased accumulation of Aβ within and around astrocytes and greater vulnerability of these cells to Aβ toxicity.
- Furthermore, PFKFB3 expression also demonstrated an increase in these mice, although at a later age (9 months) than GFAP and Aβ.
- Immunohistochemical staining showed significant reactive astrogliosis surrounding Aβ plaques with increased PFKFB3 activity in 12-month-old TgCRND8 mice, an age when AD pathology and behavioral deficits are fully manifested.
Why it matters
In cultures of human fetal astrocytes and in Alzheimer's disease transgenic mice, inhibiting or reducing PFKFB3 increased accumulation of amyloid β within and around astrocytes and made these cells more vulnerable to amyloid β toxicity. It is a laboratory and animal study and does not test any treatment, cure or prevention in people.
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Study details
- Evidence strengthLow
How this study scored 40/100
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 (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (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 | 2015 — 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 | 4 / 7 | Cited 91 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.0 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 3 / 6 | Cited 4.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jack H. Jhamandas: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Alberta: institution h-index 1,174 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25814669) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
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