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Cerebrospinal fluid profile of NPTX2 supports role of Alzheimer's disease-related inhibitory circuit dysfunction in adults with Down syndrome
Belbin O, Xiao MF, Xu D, Carmona-Iragui M, Pegueroles J, Benejam B, Videla L, Fernández S et al.. Molecular neurodegeneration, 2020-08-17
Topic: Brain proteins, microglia and lab models
Background Alzheimer's disease (AD) is the major cause of death in adults with Down syndrome (DS). There is an urgent need for objective markers of AD in the DS population to improve early diagnosis and monitor disease progression. NPTX2 has recently emerged as a promising cerebrospinal fluid (CSF) biomarker of Alzheimer-related inhibitory circuit dysfunction in sporadic AD patients. The objective of this study was to evaluate NPTX2 in the CSF of adults with DS and to explore the relationship of NPTX2 to CSF levels of the PV interneuron receptor, GluA4, and existing AD biomarkers (CSF and neuroimaging). Methods This is a cross-sectional, retrospective study of adults with DS with asymptomatic AD (aDS, n = 49), prodromal AD (pDS, n = 18) and AD dementia (dDS, n = 27). Non-trisomic controls (n = 34) and patients with sporadic AD dementia (sAD, n = 40) were included for comparison. We compared group differences in CSF NPTX2 according to clinical diagnosis and degree of intellectual disability. We determined the relationship of CSF NPTX2 levels to age, cognitive performance (CAMCOG, free and cued selective reminding, semantic verbal fluency), CSF levels of a PV-interneuron marker (GluA4) and core AD biomarkers; CSF Aβ 1-42 , CSF t-tau, cortical atrophy (magnetic resonance imaging) and glucose metabolism ([ 18 F]-fluorodeoxyglucose positron emission tomography). Results Compared to controls, mean CSF NPTX2 levels were lower in DS at all AD stages; aDS (0.6-fold, adj.p 0.07). Low CSF NPTX2 levels were associated with low GluA4 in all clinical groups; controls (r 2 = 0.2, p = 0.003), adults with DS (r 2 = 0.4, p 2 = 0.4, p 1-42 (r 2 > 0.3, p 2 > 0.3, p Conclusions Low levels of CSF NPTX2, a protein implicated in inhibitory circuit function, is common to sporadic and genetic forms of AD. CSF NPTX2 represents a promising CSF surrogate marker of early AD-related changes in adults with DS.
Key findings
- Results Compared to controls, mean CSF NPTX2 levels were lower in DS at all AD stages; aDS (0.6-fold, adj.p 0.07).
- Low CSF NPTX2 levels were associated with low GluA4 in all clinical groups; controls (r 2 = 0.2, p = 0.003), adults with DS (r 2 = 0.4, p < 0.0001) and sporadic AD (r 2 = 0.4, p < 0.0001).
Why it matters
This study found that cerebrospinal fluid levels of NPTX2 are lower in adults with Down syndrome at all stages of Alzheimer disease compared to controls. It supports NPTX2 as a potential biomarker, but it does not test any treatment or cure.
Study details
- Study designcross-sectional
- Participants49
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 49 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 | 4 / 7 | Cited 40 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.0 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 2 / 6 | Cited 3.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Juan Fortea: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32807227) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-020-00398-0
- PubMed: 32807227
- Original source →
- Free full text: Molecular Neurodegeneration →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Belbin, O., Xiao, M. F., Xu, D., Carmona-Iragui, M., Pegueroles, J., Benejam, B., et al. (2020). Cerebrospinal fluid profile of NPTX2 supports role of Alzheimer's disease-related inhibitory circuit dysfunction in adults with Down syndrome. Molecular neurodegeneration. https://doi.org/10.1186/s13024-020-00398-0
Vancouver
Belbin O, Xiao MF, Xu D, Carmona-Iragui M, Pegueroles J, Benejam B, et al. Cerebrospinal fluid profile of NPTX2 supports role of Alzheimer's disease-related inhibitory circuit dysfunction in adults with Down syndrome. Molecular neurodegeneration. 2020. doi:10.1186/s13024-020-00398-0. PMID: 32807227.
BibTeX
@article{belbin2020-32807227,
author = {Belbin, O. and Xiao, M. F. and Xu, D. and Carmona-Iragui, M. and Pegueroles, J. and Benejam, B. and Videla, L. and Fernández, S. and others},
title = {{Cerebrospinal fluid profile of NPTX2 supports role of Alzheimer's disease-related inhibitory circuit dysfunction in adults with Down syndrome}},
journal = {Molecular neurodegeneration},
year = {2020},
doi = {10.1186/s13024-020-00398-0},
pmid = {32807227},
url = {https://doi.org/10.1186/s13024-020-00398-0}
}
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