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Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ42 decrease with age, whereas NT1 tau and NfL increase
Mengel D, Liu W, Glynn RJ, Selkoe DJ, Strydom A, Lai F, Rosas HD, Torres A et al.. Alzheimer's research & therapy, 2020-03-19
Topic: Plasma and spinal-fluid biomarkers
Background Down syndrome (DS) is the most common genetic cause of Alzheimer's disease (AD), but diagnosis of AD in DS is challenging due to the intellectual disability which accompanies DS. When disease-modifying agents for AD are approved, reliable biomarkers will be required to identify when and how long people with DS should undergo treatment. Three cardinal neuropathological features characterize AD, and AD in DS-Aβ amyloid plaques, tau neurofibrillary tangles, and neuronal loss. Here, we quantified plasma biomarkers of all 3 neuropathological features in a large cohort of people with DS aged from 3 months to 68 years. Our primary aims were (1) to assess changes in the selected plasma biomarkers in DS across age, and (2) to compare biomarkers measured in DS plasma versus age- and sex-matched controls. Methods Using ultra-sensitive single molecule array (Simoa) assays, we measured 3 analytes (Aβ42, NfL, and tau) in plasmas of 100 individuals with DS and 100 age- and sex-matched controls. Tau was measured using an assay (NT1) which detects forms of tau containing at least residues 6-198. The stability of the 3 analytes was established using plasma from ten healthy volunteers collected at 6 intervals over a 5-day period. Results High Aβ42 and NT1 tau and low NfL were observed in infants. Across all ages, Aβ42 levels were higher in DS than controls. Levels of Aβ42 decreased with age in both DS and controls, but this decrease was greater in DS than controls and became prominent in the third decade of life. NT1 tau fell in adolescents and young adults, but increased in older individuals with DS. NfL levels were low in infants, children, adolescents, and young adults, but thereafter increased in DS compared to controls. Conclusions High levels of Aβ42 and tau in both young controls and DS suggest these proteins are produced by normal physiological processes, whereas the changes seen in later life are consistent with emergence of pathological alterations. These plasma biomarker results are in good agreement with prior neuropathology studies and indicate that the third and fourth decades (i.e., 20 to 40 years of age) of life are pivotal periods during which AD processes manifest in DS. Application of the assays used here to longitudinal studies of individuals with DS aged 20 to 50 years of age should further validate the use of these biomarkers, and in time may allow identification and monitoring of people with DS best suited for treatment with AD therapies.
Key findings
- Our primary aims were (1) to assess changes in the selected plasma biomarkers in DS across age, and (2) to compare biomarkers measured in DS plasma versus age- and sex-matched controls.
- Results High Aβ42 and NT1 tau and low NfL were observed in infants.
- NfL levels were low in infants, children, adolescents, and young adults, but thereafter increased in DS compared to controls.
- These plasma biomarker results are in good agreement with prior neuropathology studies and indicate that the third and fourth decades (i.e., 20 to 40 years of age) of life are pivotal periods during which AD processes manifest in DS.
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Study details
- Study designlongitudinal study
- Participants100
- Evidence strengthModerate
How this study scored 66/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for 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, 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 38 of the 58 points we could judge it on, which is 66 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 longitudinal study following the same 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 | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 100 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 (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 32192521) |
| Free to read | 2 / 2 | Free to read |
| Points | 38 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 38 of the 58 points we could judge it on is 66 out of 100. |
| Total | 66 / 100 | — |
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APA 7th
Mengel, D., Liu, W., Glynn, R. J., Selkoe, D. J., Strydom, A., Lai, F., et al. (2020). Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ42 decrease with age, whereas NT1 tau and NfL increase. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-020-00593-7
Vancouver
Mengel D, Liu W, Glynn RJ, Selkoe DJ, Strydom A, Lai F, et al. Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ42 decrease with age, whereas NT1 tau and NfL increase. Alzheimer's research & therapy. 2020. doi:10.1186/s13195-020-00593-7. PMID: 32192521.
BibTeX
@article{mengel2020-32192521,
author = {Mengel, D. and Liu, W. and Glynn, R. J. and Selkoe, D. J. and Strydom, A. and Lai, F. and Rosas, H. D. and Torres, A. and others},
title = {{Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ42 decrease with age, whereas NT1 tau and NfL increase}},
journal = {Alzheimer's research \& therapy},
year = {2020},
doi = {10.1186/s13195-020-00593-7},
pmid = {32192521},
url = {https://doi.org/10.1186/s13195-020-00593-7}
}
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