Home › Research › Down syndrome and Alzheimer's
Endosome Dysregulation in Down Syndrome: A Potential Contributor to Alzheimer Disease Pathology
Filippone A, Praticò D.. Annals of neurology, 2021-02-25
Topic: Brain proteins, microglia and lab models
Intracellular protein trafficking via the endosomes plays a key role in the maintenance of normal neuronal function. Although many diseases of the central nervous system exhibit specific pathological hallmarks, abnormalities of the endosome system are common traits for several of them, including Alzheimer disease (AD). Three main routes originate from the endosomes: the recycling, degradation, and retrograde pathways. Studies have shown that the majority of Down syndrome subjects develop AD pathology and manifest altered morphology and number of endosomes, and abnormalities in lysosome acidification and exosome secretion, suggesting that dysfunction of one of these pathways could play a functional role in the AD-like phenotype of the syndrome. Two of the major endosomal routes are mediated by the retromer complex, a multimeric system responsible for transport of cargo from the endosome to the trans-Golgi network or to the cell membrane. Recently, a new endosome system structurally related to the retromer, called "retriever," has been reported. Whereas we know a great deal about the neuropathophysiology of the retromer complex, no precise pathogenic role for the retriever has yet been identified. Here, we will review the neurobiology of the endosome system and its role as key player in the development of AD-like pathology in Down syndrome. Additionally, we will discuss current knowledge on these two main endosome systems, retromer and retriever, and their potential as novel therapeutic targets. ANN NEUROL 2021;90:4-14.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Filippone, A., & Praticò, D. (2021). Endosome Dysregulation in Down Syndrome: A Potential Contributor to Alzheimer Disease Pathology. Annals of neurology. https://doi.org/10.1002/ana.26042
Vancouver
Filippone A, Praticò D. Endosome Dysregulation in Down Syndrome: A Potential Contributor to Alzheimer Disease Pathology. Annals of neurology. 2021. doi:10.1002/ana.26042. PMID: 33547827.
BibTeX
@article{filippone2021-33547827,
author = {Filippone, A. and Praticò, D.},
title = {{Endosome Dysregulation in Down Syndrome: A Potential Contributor to Alzheimer Disease Pathology}},
journal = {Annals of neurology},
year = {2021},
doi = {10.1002/ana.26042},
pmid = {33547827},
url = {https://doi.org/10.1002/ana.26042}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Studies have shown that the majority of Down syndrome subjects develop AD pathology and manifest altered morphology and number of endosomes, and abnormalities in lysosome acidification and exosome secretion, suggesting that dysfunction of one of these pathways could play a functional role in the AD-like phenotype of the syndrome.
Why it matters
This review describes how the endosome system, which moves proteins inside cells, is abnormal in Down syndrome and may contribute to Alzheimer's-like pathology. It discusses possible mechanisms but reports no treatment or cure.
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 2021 — 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 | 3 / 7 | Cited 20 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.9 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 2 / 6 | Cited 1.3× 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 | 1 / 4 | Cited 10 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Domenico Praticò: h-index 92 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Temple University: institution h-index 742 (OpenAlex) |
| Multi-centre 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 33547827) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Related studies in Down syndrome and Alzheimer's
Also tagged “down”
527 studies in the library carry the topic tag “down”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 527 tagged studies.