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Metabolic Syndrome and the Cellular Phase of Alzheimer's Disease
S Pugazhenthi. Progress in molecular biology and translational science, 2017-02-04
Topic: Gut, metabolism and diet
Alzheimer's disease (AD) is characterized by cognitive dysfunction and progressive neurodegeneration. The major hallmarks of AD pathology are amyloid plaques and neurofibrillary tangles. However, AD often coexists with other brain microvascular lesions caused by comorbidities, including obesity, diabetes, hypertension, and cardiovascular diseases. The risk factors for these comorbidities are collectively referred to as metabolic syndrome (MetS). Clinical AD is preceded by decades of prodromal cellular phase. During this asymptomatic phase, systemic changes caused by MetS can play critical roles in driving neuroinflammation, an important cause of AD pathogenesis. Studies of MetS and AD have traditionally remained in distinct domains. The cross talk between MetS and the cellular phase of AD is an important area to be investigated. AD risk factors identified by genome-wide association studies (GWAS) have strongly suggested the role of microglia, the resident immune cells of the brain, in AD pathogenesis. Microglial dysregulation is caused not only by CNS-intrinsic factors but also by systemic changes. MetS appears to cause brain mitochondrial dysfunction through a defective NAD+-sirtuin pathway. Sirtuins are a family of seven proteins that are involved in longevity and inflammation. Among them, SIRT3 is exclusively present in mitochondria, playing a significant role in metabolic adaptation. SIRT3 deacetylates and activates key metabolic enzymes and transcriptional regulators, utilizing NAD+ in the process. MetS could prime microglia through the interface of blood-brain barrier (BBB). Age-dependent breakdown of the BBB has been reported in human subjects. The neurovascular unit at BBB consists of brain microvascular endothelial cells, end feet of astrocytes, and pericytes. Therapeutic targeting of the sirtuin pathway in AD with coexisting pathologies has the potential to produce profoundly beneficial effects in improving mitochondrial function and decreasing neuroinflammation.
Key findings
- Among them, SIRT3 is exclusively present in mitochondria, playing a significant role in metabolic adaptation.
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Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / 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, multi-centre collaboration and free to read, so those were left out: it earned 22 of the 56 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Progress in molecular biology and translational science) |
| 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 | 2 / 5 | 2017 — within 10 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) |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28253987) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 22 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 22 of the 56 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Pugazhenthi, S. (2017). Metabolic Syndrome and the Cellular Phase of Alzheimer's Disease. Progress in molecular biology and translational science. https://doi.org/10.1016/bs.pmbts.2016.12.016
Vancouver
Pugazhenthi S. Metabolic Syndrome and the Cellular Phase of Alzheimer's Disease. Progress in molecular biology and translational science. 2017. doi:10.1016/bs.pmbts.2016.12.016. PMID: 28253987.
BibTeX
@article{pugazhenthi2017-28253987,
author = {Pugazhenthi, S},
title = {{Metabolic Syndrome and the Cellular Phase of Alzheimer's Disease}},
journal = {Progress in molecular biology and translational science},
year = {2017},
doi = {10.1016/bs.pmbts.2016.12.016},
pmid = {28253987},
url = {https://doi.org/10.1016/bs.pmbts.2016.12.016}
}
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