Depression as a risk factor for Alzheimer's disease: Genes, steroids, cytokines and neurogenesis - What do we need to know?
Herbert J, Lucassen PJ.. Frontiers in neuroendocrinology, 2015-12-30
Topic: Amyloid, tau and blood-test diagnosis
Depression (MDD) is prodromal to, and a component of, Alzheimer's disease (AD): it may also be a trigger for incipient AD. MDD is not a unitary disorder, so there may be particular subtypes of early life MDD that pose independent high risks for later AD, though the identification of these subtypes is problematical. There may either be a common pathological event underlying both MDD and AD, or MDD may sensitize the brain to a second event ('hit') that precipitates AD. MDD may also accelerate brain ageing, including altered DNA methylation, increased cortisol but decreasing DHEA and thus the risk for AD. So far, genes predicting AD (e.g. APOEε4) are not risk factors for MDD, and those implicated in MDD (e.g. SLC6A4) are not risks for AD, so a common genetic predisposition looks unlikely. There is as yet no strong indication that an epigenetic event occurs during some forms of MDD that predisposes to later AD, though the evidence is limited. Glucocorticoids (GCs) are disturbed in some cases of MDD and in AD. GCs have marked degenerative actions on the hippocampus, a site of early β-amyloid deposition, and rare genetic variants of GC-regulating enzymes (e.g. 11β-HSD) predispose to AD. GCs also inhibit hippocampal neurogenesis and plasticity, and thus episodic memory, a core symptom of AD. Disordered GCs in MDD may inhibit neurogenesis, but the contribution of diminished neurogenesis to the onset or progression of AD is still debated. GCs and cytokines also reduce BDNF, implicated in both MDD and AD and hippocampal neurogenesis, reinforcing the notion that those cases of MDD with disordered GCs may be a risk for AD. Cytokines, including IL1β, IL6 and TNFα, are increased in the blood in some cases of MDD. They also reduce hippocampal neurogenesis, and increased cytokines are a known risk for later AD. Inflammatory changes occur in both MDD and AD (e.g. raised CRP, TNFα). Both cytokines and GCs can have pro-inflammatory actions in the brain. Inflammation (e.g. microglial activation) may be a common link, but this has not been systematically investigated. We lack substantial, rigorous and comprehensive follow-up studies to better identify possible subtypes of MDD that may represent a major predictor for later AD. This would enable specific interventions during critical episodes of these subtypes of MDD that should reduce this substantial risk.
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APA 7th
Herbert, J., & Lucassen, P. J. (2016). Depression as a risk factor for Alzheimer's disease: Genes, steroids, cytokines and neurogenesis - What do we need to know? Frontiers in neuroendocrinology. https://doi.org/10.1016/j.yfrne.2015.12.001
Vancouver
Herbert J, Lucassen PJ. Depression as a risk factor for Alzheimer's disease: Genes, steroids, cytokines and neurogenesis - What do we need to know? Frontiers in neuroendocrinology. 2016. doi:10.1016/j.yfrne.2015.12.001. PMID: 26746105.
BibTeX
@article{herbert2016-26746105,
author = {Herbert, J. and Lucassen, P. J.},
title = {{Depression as a risk factor for Alzheimer's disease: Genes, steroids, cytokines and neurogenesis - What do we need to know?}},
journal = {Frontiers in neuroendocrinology},
year = {2016},
doi = {10.1016/j.yfrne.2015.12.001},
pmid = {26746105},
url = {https://doi.org/10.1016/j.yfrne.2015.12.001}
}
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Key findings
- Inflammatory changes occur in both MDD and AD (e.g. raised CRP, TNFα).
- Both cytokines and GCs can have pro-inflammatory actions in the brain.
- Inflammation (e.g. microglial activation) may be a common link, but this has not been systematically investigated.
- We lack substantial, rigorous and comprehensive follow-up studies to better identify possible subtypes of MDD that may represent a major predictor for later AD.
- This would enable specific interventions during critical episodes of these subtypes of MDD that should reduce this substantial risk.
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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 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 and multi-centre 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 (Frontiers in neuroendocrinology) |
| 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 | 2016 — 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) |
| 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 26746105) |
| 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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