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From Amyloid to Synaptic Dysfunction: Biomarker-Driven Insights into Alzheimer's Disease
Luisa Agnello, Caterina Maria Gambino, Anna Maria Ciaccio, Francesco Cacciabaudo, Davide Massa, Anna Masucci, Martina Tamburello, Roberta Vassallo et al.. Current issues in molecular biology, 2025-07-22
Topic: Plasma and spinal-fluid biomarkers
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and represents a major public health challenge. With increasing life expectancy, the incidence of AD has also increased, highlighting the need for early diagnosis and improved monitoring. Traditionally, diagnosis has relied on clinical symptoms and neuroimaging; however, the introduction of biomarkers has revolutionized disease assessment. Traditional biomarkers, including the Aβ42/Aβ40 ratio, phosphorylated tau (p-Tau181, p-Tau217, and p-Tau231), total tau (t-tau), and neurofilament light chain (NfL), are fundamental for staging AD progression. Updated guidelines introduced the ATX(N) model, which extends biomarker classification to include additional promising biomarkers, such as SNAP-25, YKL-40, GAP-43, VILIP-1, progranulin (PGRN), TREM2, IGF-1, hFABP, MCP-1, TDP-43, and BDNF. Recent advancements have allowed for the detection of these biomarkers not only in CSF but also in plasma and neuron-derived exosomes, offering less invasive and more accessible diagnostic options. This review explores established and emerging biomarkers and emphasizes their roles in early diagnosis, patient stratification, and precision medicine.
Key findings
- Traditionally, diagnosis has relied on clinical symptoms and neuroimaging; however, the introduction of biomarkers has revolutionized disease assessment.
- Traditional biomarkers, including the Aβ42/Aβ40 ratio, phosphorylated tau (p-Tau181, p-Tau217, and p-Tau231), total tau (t-tau), and neurofilament light chain (NfL), are fundamental for staging AD progression.
- Updated guidelines introduced the ATX(N) model, which extends biomarker classification to include additional promising biomarkers, such as SNAP-25, YKL-40, GAP-43, VILIP-1, progranulin (PGRN), TREM2, IGF-1, hFABP, MCP-1, TDP-43, and BDNF.
- Recent advancements have allowed for the detection of these biomarkers not only in CSF but also in plasma and neuron-derived exosomes, offering less invasive and more accessible diagnostic options.
- This review explores established and emerging biomarkers and emphasizes their roles in early diagnosis, patient stratification, and precision medicine.
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Study details
- Evidence strengthLow
How this study scored 43/100
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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Current issues in molecular biology) |
| 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 | 4 / 5 | 2025 — within 3 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 40864734) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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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
Agnello, L., Gambino, C. M., Ciaccio, A. M., Cacciabaudo, F., Massa, D., Masucci, A., et al. (2025). From Amyloid to Synaptic Dysfunction: Biomarker-Driven Insights into Alzheimer's Disease. Current issues in molecular biology. https://doi.org/10.3390/cimb47080580
Vancouver
Agnello L, Gambino CM, Ciaccio AM, Cacciabaudo F, Massa D, Masucci A, et al. From Amyloid to Synaptic Dysfunction: Biomarker-Driven Insights into Alzheimer's Disease. Current issues in molecular biology. 2025. doi:10.3390/cimb47080580. PMID: 40864734.
BibTeX
@article{agnello2025-40864734,
author = {Agnello, Luisa and Gambino, Caterina Maria and Ciaccio, Anna Maria and Cacciabaudo, Francesco and Massa, Davide and Masucci, Anna and Tamburello, Martina and Vassallo, Roberta and others},
title = {{From Amyloid to Synaptic Dysfunction: Biomarker-Driven Insights into Alzheimer's Disease}},
journal = {Current issues in molecular biology},
year = {2025},
doi = {10.3390/cimb47080580},
pmid = {40864734},
url = {https://doi.org/10.3390/cimb47080580}
}
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