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The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer's disease
Franzmeier N, Ren J, Damm A, Monté-Rubio G, Boada M, Ruiz A, Ramirez A, Jessen F et al.. Molecular psychiatry, 2019-03-21
Topic: Brain proteins, microglia and lab models
In Alzheimer's disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF Val66Met ) is associated with worse impact of primary AD pathology (beta-amyloid, Aβ) on neurodegeneration and cognitive decline, rendering BDNF Val66Met an important modulating factor of cognitive impairment in AD. However, the effect of BDNF Val66Met on functional networks that may underlie cognitive impairment in AD is poorly understood. Using a cross-validation approach, we first explored in subjects with autosomal dominant AD (ADAD) from the Dominantly Inherited Alzheimer Network (DIAN) the effect of BDNF Val66Met on resting-state fMRI assessed functional networks. In seed-based connectivity analysis of six major large-scale networks, we found a stronger decrease of hippocampus (seed) to medial-frontal connectivity in the BDNF Val66Met carriers compared to BDNF Val homozogytes. BDNF Val66Met was not associated with connectivity in any other networks. Next, we tested whether the finding of more pronounced decrease in hippocampal-medial-frontal connectivity in BDNF Val66Met could be also found in elderly subjects with sporadically occurring Aβ, including a group with subjective cognitive decline (N = 149, FACEHBI study) and a group ranging from preclinical to AD dementia (N = 114, DELCODE study). In both of these independently recruited groups, BDNF Val66Met was associated with a stronger effect of more abnormal Aβ-levels (assessed by biofluid-assay or amyloid-PET) on hippocampal-medial-frontal connectivity decreases, controlled for hippocampus volume and other confounds. Lower hippocampal-medial-frontal connectivity was associated with lower global cognitive performance in the DIAN and DELCODE studies. Together these results suggest that BDNF Val66Met is selectively associated with a higher vulnerability of hippocampus-frontal connectivity to primary AD pathology, resulting in greater AD-related cognitive impairment.
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APA 7th
Franzmeier, N., Ren, J., Damm, A., Monté-Rubio, G., Boada, M., Ruiz, A., et al. (2021). The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer's disease. Molecular psychiatry. https://doi.org/10.1038/s41380-019-0404-6
Vancouver
Franzmeier N, Ren J, Damm A, Monté-Rubio G, Boada M, Ruiz A, et al. The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer's disease. Molecular psychiatry. 2021. doi:10.1038/s41380-019-0404-6. PMID: 30899092.
BibTeX
@article{franzmeier2021-30899092,
author = {Franzmeier, N. and Ren, J. and Damm, A. and Monté-Rubio, G. and Boada, M. and Ruiz, A. and Ramirez, A. and Jessen, F. and others},
title = {{The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer's disease}},
journal = {Molecular psychiatry},
year = {2021},
doi = {10.1038/s41380-019-0404-6},
pmid = {30899092},
url = {https://doi.org/10.1038/s41380-019-0404-6}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- In Alzheimer's disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF Val66Met ) is associated with worse impact of primary AD pathology (beta-amyloid, Aβ) on neurodegeneration and cognitive decline, rendering BDNF Val66Met an important modulating factor of cognitive impairment in AD.
- In seed-based connectivity analysis of six major large-scale networks, we found a stronger decrease of hippocampus (seed) to medial-frontal connectivity in the BDNF Val66Met carriers compared to BDNF Val homozogytes.
- BDNF Val66Met was not associated with connectivity in any other networks.
- In both of these independently recruited groups, BDNF Val66Met was associated with a stronger effect of more abnormal Aβ-levels (assessed by biofluid-assay or amyloid-PET) on hippocampal-medial-frontal connectivity decreases, controlled for hippocampus volume and other confounds.
- Lower hippocampal-medial-frontal connectivity was associated with lower global cognitive performance in the DIAN and DELCODE studies.
Why it matters
This study found that the BDNF Val66Met variant was linked to a stronger decrease in hippocampus to medial-frontal connectivity in people with Alzheimer's disease pathology. It concerns how a genetic variant modulates brain networks and does not test any treatment, cure or prevention.
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Study details
- Participants149
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, effect reported 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, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 31 of the 64 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 149 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (OpenAlex dates this DOI to 2019, the record says 2021; OpenAlex values not used) — 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 | 1 / 6 | Cited by 2 other studies in this library |
| 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 30899092) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 64 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 31 of the 64 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
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