The DOI matches its Crossref record; 46 of the 47 references it cites were found in a registry or an index.
Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome
Open accessAbstract
Introduction: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non‐AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid β (Aβ) peptides and phosphorylated‐tau in neuronal exosomes may document preclinical AD. Methods: AD neuropathogenic proteins Aβ 1–42, P‐T181‐tau, and P‐S396‐tau were quantified by enzyme‐linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age‐matched controls. Results: Neuronal exosome levels of Aβ 1–42, P‐T181‐tau, and P‐S396‐tau were significantly elevated in individuals with DS compared with age‐matched controls at all ages beginning in childhood. No significant gender differences were observed. Discussion: These early increases in Aβ 1–42, P‐T181‐tau, and P‐S396‐tau in individuals with DS may provide a basis for early intervention as targeted treatments become available.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The rationale for using plasma biomarkers as proxies for brain processes [173] has been demonstrated for multiple neurodegenerative diseases [174, 175].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [174]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Alzheimer’s disease β-amyloid peptides are released in association with exosomes
Rajendran, L., Honsho, M., Zahn, T. R., Keller, P., Geiger, K. D., Verkade, P., & Simons, K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603838103 · Cited by 1,343
Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome
Wisniewski, K. E., Wisniewski, H. M., & Wen, G. Y. (1985) · Annals of Neurology · doi:10.1002/ana.410170310 · Cited by 1,159
Fiandaca, M. S., Kapogiannis, D., Mapstone, M., Boxer, A., Eitan, E., Schwartz, J. B., Abner, E. L., Petersen, R. C., Federoff, H. J., Miller, B. L., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.06.008 · Cited by 959
Self-citationHaass, C., Lemere, C. A., Capell, A., Citron, M., Seubert, P., Schenk, D., Lannfelt, L., & Selkoe, D. J. (1995) · Nature Medicine · doi:10.1038/nm1295-1291 · Cited by 592
Lemere, C. A., Blusztajn, J. K., Yamaguchi, H., Wisniewski, T., Saido, T. C., & Selkoe, D. J. (1996) · Neurobiology of Disease · doi:10.1006/nbdi.1996.0003 · Cited by 584 · cited 1×
“Amyloid pathology has been observed as early as 15 years of age in postmortem brain samples from individuals with DS [4].”
BackgroundA genetic cause of Alzheimer disease: mechanistic insights from Down syndrome
Wiseman, F. K., Al-Janabi, T., Hardy, J., Karmiloff-Smith, A., Nizetic, D., Tybulewicz, V. L. J., Fisher, E. M. C., & Strydom, A. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3983 · Cited by 562
Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
Jaunmuktane, Z., Mead, S., Ellis, M., Wadsworth, J. D. F., Nicoll, A. J., Kenny, J., Launchbury, F., Linehan, J., Richard-Loendt, A., Walker, A. S., et al. (2015) · Nature · doi:10.1038/nature15369 · Cited by 518
Mann, D. M. A., & Esiri, M. M. (1989) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(89)90019-1 · Cited by 471
Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease
Goetzl, E. J., Boxer, A., Schwartz, J. B., Abner, E. L., Petersen, R. C., Miller, B. L., & Kapogiannis, D. (2015) · Neurology · doi:10.1212/wnl.0000000000001702 · Cited by 446
Self-citationLongitudinal Change in CSF Biomarkers in Autosomal-Dominant Alzheimer’s Disease
Fagan, A. M., Xiong, C., Jasielec, M. S., Bateman, R. J., Goate, A. M., Benzinger, T. L. S., Ghetti, B., Martins, R. N., Masters, C. L., Mayeux, R., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007901 · Cited by 434
Cited by
Sorted by citations
Items 101–129 of 129
Melnik, M., Miyoshi, E., Ma, R., Corrada, M. M., Kawas, C. H., Bohannan, R. C., Caraway, C. A., Miller, C. A., Hinman, J. D., John, V., et al. (2024) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2024.110137 · Cited by 8
Cell type characterization of spatiotemporal gene co-expression modules in Down syndrome brain
Seol, S., Kwon, J., & Kang, H. J. (2022) · iScience · doi:10.1016/j.isci.2022.105884 · Cited by 8
Ledreux, A., Carmona‐Iragui, M., Videla, L., Benejam, B., Barroeta, I., Lleó, A., Alcolea, D. A., & Fortea, J. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70380 · Cited by 7
Self-citationAlzheimer’s Disease-related Biomarkers in Aging Adults with Down Syndrome: Systematic Review
Bram, J. M. D. F., Talib, L. L., Joaquim, H. P. G., Carvalho, C. L., Gattaz, W. F., & Forlenza, O. V. (2019) · Current Psychiatry Research and Reviews · doi:10.2174/1573400515666190122152855 · Cited by 7
Işık, M., Sari, H. K., Çağlayan, M. G., Yılmaz, R., & Derkuş, B. (2025) · European Journal of Neuroscience · doi:10.1111/ejn.70090 · Cited by 4
Domenico, F. D., Greco, V., Tramutola, A., Rataj-Baniowska, M., Barone, E., Lanzillotta, C., Pieroni, L., Butterfield, D. A., Hérault, Y., Pagnotta, S. E., et al. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05432-0 · Cited by 5
Extracellular Vesicles in Alzheimer’s Disease: Mechanisms, Biomarkers, and Therapeutic Engineering
Wang, L., Mao, L., & Zong, X. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27093974 · Cited by 4
Baek, S., Lee, J. C., Byun, B. H., Park, S. Y., Ha, J. H., Lee, K. C., Yang, S., Lee, J., Hong, S., Han, G., et al. (2025) · Experimental Neurobiology · doi:10.5607/en25008 · Cited by 3
Sharma, R., Song, B. S., Rane, R., Paul, D., Singh, B., Verma, T., Mishra, A., Karan, A., & Song, J. J. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119297 · Cited by 2
Zare, H., Kasdorf, M., & Nik, A. B. (2024) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2024.103982 · Cited by 2
Valle‐Tamayo, N., Aranha, M. R., Pérez‐González, R., Serrano‐Requena, S., Videla, L., Barroeta, I., Benejam, B., Chiva‐Blanch, G., Jiménez, A., Busciglio, J. A., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70137 · Cited by 2
Self-citationFluid biomarkers for Alzheimer's disease in Down syndrome: Current status and novel trends
Iulita, M. F., Granholm, A., Carmona‐Iragui, M., Hamlett, E. D., Fortea, J., & Ledreux, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-818845-3.00010-4 · Cited by 2
Self-citationAlzheimer's neuropathology in Down syndrome: From gestation to old age
Mufson, E. J., Miguel, J. C., & Perez, S. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-818845-3.00011-6 · Cited by 2
Self-citationPetersen, M. E., Gross, T. J., O’Bryant, S. E., & Mapstone, M. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-818845-3.00018-9 · Cited by 2
Lehrich, B. M., Liang, Y., & Fiandaca, M. S. (2024) · Springer eBooks · doi:10.1007/978-3-030-80662-0_4 · Cited by 1
The cholinotrophic system in Down syndrome
Mufson, E. J., & Perez, S. E. (2025) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19088-9.00017-2 · Cited by 1
Self-citationBelali, R., & Sameri, M. J. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.153533 · Cited by 1
Puthiyattil, N., Varughese, D., Mani, B. M., Babu, R. S., Nair, K. S., George, R. L., Ramitha, P. A., Dogra, N., Mathew, M., Varghese, M. T., et al. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103178 · Cited by 2
Biomarkers of Cognitive Decline and Dementia in Down Syndrome
Pais, M. V., Talib, L. L., & Forlenza, O. V. (2023) · Springer eBooks · doi:10.1007/978-3-031-43356-6_12 · Cited by 1
McKeever, P. M. (2018) · TSpace (University of Toronto)
Хаспеков, Л. Г., & Yakovlev, A. A. (2023) · Нейрохимия · doi:10.31857/s1027813323010089
Grossberg, A. N. (2024) · Digital Commons - DU (University of Denver) · doi:10.56902/etdcrp.2024.14
Extracellular Vesicles as Biomarkers of Alzheimer Disease and Related Dementias
Mianoor, Z., Phelps, J., & Badhwar, A. (2025) · Springer eBooks · doi:10.1007/978-3-031-80849-4_18
Sharma, R. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152881
Lemoine, L., Ledreux, A., Mufson, E. J., Perez, S. E., Simic, G., Doran, E. W., Lott, I. T., Carroll, S., Bharani, K., Thomas, S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13272076
Self-citationExtracellular vesicles in neurodegenerative diseases: A new frontier in diagnosis and therapy
Mohammad, S. I., Vasudevan, A., Oriquat, G., Gajjar, T. B., Hanumanthayya, M., Shukla, S. K., Tailor, N. K., Baig, M. R., Fadaam, O., & Abdul, A. S. (2026) · Behavioural Brain Research · doi:10.1016/j.bbr.2026.116455
The Roles and Uses of Extracellular Vesicles in Neuroimmunologic Diseases
Kammeyer, R., & Coughlan, C. M. (2026) · Journal of Neuroscience · doi:10.1523/jneurosci.2310-25.2026
Metadata
- Authors
- Hamlett, E. D., Goetzl, E. J., Ledreux, A., Vasilevko, V., Boger, H. A., LaRosa, A., Clark, D., Carroll, S. L., Carmona‐Iragui, M., Fortea, J., Mufson, E. J., Sabbagh, M., Mohammed, A. H., Hartley, D., Doran, E., Lott, I. T., & Granholm, A.
- Affiliations
- University of Denver (US)
- University of California, San Francisco (US)
- University of California, Irvine (US)
- Medical University of South Carolina (US)
- Hospital de Sant Pau (ES)
- Barrow Neurological Institute (US)
- Linnaeus University (SE)
- Alzheimer's Association (US)
- Corresponding author
- Granholm, Ann‐Charlotte
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-10-15
- Volume
- 13
- Issue
- 5
- Pages
- 541-549
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC5812672
- OpenAlex
- W2537024319
- Cited by
- 129
- References
- 47
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 9 · 2023: 6 · 2022: 7 · 2021: 19 · 2020: 17 · 2019: 25 · 2018: 15 · 2017: 9
- FWCI
- 13.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - DU (University of Denver) (submittedVersion)
- Funders
- National Institutes of Health (R01AG 21912, R01HD065160, RO1AG04375, PO1AG14449)
- National Center for Research Resources
- National Center for Advancing Translational Sciences (UL1 TR000153)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- Down syndrome, Alzheimer's disease
- MeSH terms
- Adolescent, Alzheimer Disease, Down Syndrome, Female, Humans, Male, Middle Aged, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Exosomes, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review