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Plasma NfL is associated with the APOE ε4 allele, brain imaging measurements of neurodegeneration, and lower recall memory scores in cognitively unimpaired late-middle-aged and older adults
Malek-Ahmadi M, Su Y, Ghisays V, Luo J, Devadas V, Chen Y, Lee W, Protas H et al.. Alzheimer's research & therapy, 2023-04-10
Topic: Brain proteins, microglia and lab models
Background Plasma neurofilament light (NfL) is an indicator of neurodegeneration and/or neuroaxonal injury in persons with Alzheimer's disease (AD) and a wide range of other neurological disorders. Here, we characterized and compared plasma NfL concentrations in cognitively unimpaired (CU) late-middle-aged and older adults with two, one, or no copies of the APOE ε4 allele, the major genetic risk factor for AD. We then assessed plasma NfL associations with brain imaging measurements of AD-related neurodegeneration (hippocampal atrophy and a hypometabolic convergence index [HCI]), brain imaging measurements of amyloid-β plaque burden, tau tangle burden and white matter hyperintensity volume (WMHV), and delayed and total recall memory scores. Methods Plasma NfL concentrations were measured in 543 CU 69 ± 9 year-old participants in the Arizona APOE Cohort Study, including 66 APOE ε4 homozygotes (HM), 165 heterozygotes (HT), and 312 non-carriers (NC). Robust regression models were used to characterize plasma NfL associations with APOE ε4 allelic dose before and after adjustment for age, sex, and education. They were also used to characterize plasma NfL associations with MRI-based hippocampal volume and WMHV measurements, an FDG PET-based HCI, mean cortical PiB PET measurements of amyloid-β plaque burden and meta-region-of-interest (meta-ROI) flortaucipir PET measurements of tau tangle burden, and Auditory Verbal Learning Test (AVLT) Delayed and Total Recall Memory scores. Results After the adjustments noted above, plasma NfL levels were significantly greater in APOE ε4 homozygotes and heterozygotes than non-carriers and significantly associated with smaller hippocampal volumes (r = - 0.43), greater tangle burden in the entorhinal cortex and inferior temporal lobes (r = 0.49, r = 0.52, respectively), and lower delayed (r = - 0.27), and total (r = - 0.27) recall memory scores (p < 0.001). NfL levels were not significantly associated with PET measurements of amyloid-β plaque or total tangle burden. Conclusions Plasma NfL concentrations are associated with the APOE ε4 allele, brain imaging biomarkers of neurodegeneration, and less good recall memory in CU late-middle-aged and older adults, supporting its value as an indicator of neurodegeneration in the preclinical study of AD.
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APA 7th
Malek-Ahmadi, M., Su, Y., Ghisays, V., Luo, J., Devadas, V., Chen, Y., et al. (2023). Plasma NfL is associated with the APOE ε4 allele, brain imaging measurements of neurodegeneration, and lower recall memory scores in cognitively unimpaired late-middle-aged and older adults. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-023-01221-w
Vancouver
Malek-Ahmadi M, Su Y, Ghisays V, Luo J, Devadas V, Chen Y, et al. Plasma NfL is associated with the APOE ε4 allele, brain imaging measurements of neurodegeneration, and lower recall memory scores in cognitively unimpaired late-middle-aged and older adults. Alzheimer's research & therapy. 2023. doi:10.1186/s13195-023-01221-w. PMID: 37038190.
BibTeX
@article{malekahmadi2023-37038190,
author = {Malek-Ahmadi, M. and Su, Y. and Ghisays, V. and Luo, J. and Devadas, V. and Chen, Y. and Lee, W. and Protas, H. and others},
title = {{Plasma NfL is associated with the APOE ε4 allele, brain imaging measurements of neurodegeneration, and lower recall memory scores in cognitively unimpaired late-middle-aged and older adults}},
journal = {Alzheimer's research \& therapy},
year = {2023},
doi = {10.1186/s13195-023-01221-w},
pmid = {37038190},
url = {https://doi.org/10.1186/s13195-023-01221-w}
}
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Key findings
- Results After the adjustments noted above, plasma NfL levels were significantly greater in APOE ε4 homozygotes and heterozygotes than non-carriers and significantly associated with smaller hippocampal volumes (r = - 0.43), greater tangle burden in the entorhinal cortex and inferior temporal lobes (r = 0.49, r = 0.52, respectively), and lower delayed (r = - 0.27), and total (r = - 0.27) recall memory scores (p < 0.001).
- NfL levels were not significantly associated with PET measurements of amyloid-β plaque or total tangle burden.
- Conclusions Plasma NfL concentrations are associated with the APOE ε4 allele, brain imaging biomarkers of neurodegeneration, and less good recall memory in CU late-middle-aged and older adults, supporting its value as an indicator of neurodegeneration in the preclinical study of AD.
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Study details
- Study designcohort study
- Evidence strengthModerate
How this study scored 59/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for 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 34 of the 58 points we could judge it on, which is 59 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 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 37038190) |
| Free to read | 2 / 2 | Free to read |
| Points | 34 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 34 of the 58 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
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