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Beyond amyloid: Immune, cerebrovascular, and metabolic contributions to Alzheimer disease in people with Down syndrome
Martini AC, Gross TJ, Head E, Mapstone M.. Neuron, 2022-04-25
Topic: Amyloid, tau and blood-test diagnosis
People with Down syndrome (DS) have increased risk of Alzheimer disease (AD), presumably conferred through genetic predispositions arising from trisomy 21. These predispositions necessarily include triplication of the amyloid precursor protein (APP), but also other Ch21 genes that confer risk directly or through interactions with genes on other chromosomes. We discuss evidence that multiple genes on chromosome 21 are associated with metabolic dysfunction in DS. The resulting dysregulated pathways involve the immune system, leading to chronic inflammation; the cerebrovascular system, leading to disruption of the blood brain barrier (BBB); and cellular energy metabolism, promoting increased oxidative stress. In combination, these disruptions may produce a precarious biological milieu that, in the presence of accumulating amyloid, drives the pathophysiological cascade of AD in people with DS. Critically, mechanistic drivers of this dysfunction may be targetable in future clinical trials of pharmaceutical and/or lifestyle interventions.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Martini, A. C., Gross, T. J., Head, E., & Mapstone, M. (2022). Beyond amyloid: Immune, cerebrovascular, and metabolic contributions to Alzheimer disease in people with Down syndrome. Neuron. https://doi.org/10.1016/j.neuron.2022.04.001
Vancouver
Martini AC, Gross TJ, Head E, Mapstone M. Beyond amyloid: Immune, cerebrovascular, and metabolic contributions to Alzheimer disease in people with Down syndrome. Neuron. 2022. doi:10.1016/j.neuron.2022.04.001. PMID: 35472307.
BibTeX
@article{martini2022-35472307,
author = {Martini, A. C. and Gross, T. J. and Head, E. and Mapstone, M.},
title = {{Beyond amyloid: Immune, cerebrovascular, and metabolic contributions to Alzheimer disease in people with Down syndrome}},
journal = {Neuron},
year = {2022},
doi = {10.1016/j.neuron.2022.04.001},
pmid = {35472307},
url = {https://doi.org/10.1016/j.neuron.2022.04.001}
}
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Key findings
- People with Down syndrome (DS) have increased risk of Alzheimer disease (AD), presumably conferred through genetic predispositions arising from trisomy 21.
- We discuss evidence that multiple genes on chromosome 21 are associated with metabolic dysfunction in DS.
Why it matters
This review discusses how genes on chromosome 21 beyond amyloid precursor protein may contribute to Alzheimer's disease in Down syndrome through immune, blood vessel, and metabolic problems. The authors suggest these pathways could be targets for future drug or lifestyle trials, but no intervention was tested here.
Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuron) |
| Journal's citation record | 4 / 4 | Neuron: journal h-index 689 (OpenAlex, 2026-10-29) |
| 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 | 2022 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 27 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.5 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 4.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Mark E. Mapstone: h-index 42 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Irvine: institution h-index 1,195 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35472307) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
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