The DOI matches its Crossref record; 159 of the 160 references it cites were found in a registry or an index.
Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology
Open accessAbstract
Chromosome 21, triplicated in Down Syndrome, contains several genes that are thought to play a critical role in the development of AD neuropathology. The overexpression of the gene for the amyloid precursor protein (APP), on chromosome 21, leads to early onset beta-amyloid (Aβ) plaques in DS. In addition to Aβ accumulation, middle-aged people with DS develop neurofibrillary tangles, cerebrovascular pathology, white matter pathology, oxidative damage, neuroinflammation and neuron loss. There is also evidence of potential compensatory responses in DS that benefit the brain and delay the onset of dementia after there is sufficient neuropathology for a diagnosis of AD. This review describes some of the existing literature and also highlights gaps in our knowledge regarding AD neuropathology in DS. It will be critical in the future to develop networked brain banks with standardized collection procedures to fully characterize the regional and temporal pathological events associated with aging in DS. As more information is acquired regarding AD evolution in DS, there will be opportunities to develop interventions that are age-appropriate to delay AD in DS.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“There is substantial evidence of neuropathology from early in life in DS,6,9,10,21 including defects in neuronal development, an increased ratio of inhibitory to excitatory neurons, alterations in neuronal dendritic spines dynamics, activation of microglia, astrocyte reactivity, and elevated production of inflammatory cytokines in the brain.22,23,24,25”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Individuals with Down syndrome (DS), caused by trisomy of chromosome 21 (chr21, T21), are strongly predisposed to Alzheimer’s disease (AD), due to triplication of the APP gene, with ∼100% penetrance of AD brain pathology by age 40 and variable onset of dementia thereafter.”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [6]
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
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064
Self-citationHearing loss and cognitive decline in older adults
Lin, F. R., Yaffe, K., Xia, J., Xue, Q.-L., Harris, T. B., Purchase-Helzner, E., Satterfield, S., Ayonayon, H. N., Ferrucci, L., Simonsick, E. M., et al. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.1868 · Cited by 4,017
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506
Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.
Griffin, W. S., Stanley, L. C., Ling, C., White, L., MacLeod, V, Perrot, L. J., White, C. L., & Araoz, C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.19.7611 · Cited by 1,777
Research works printed but not linked: 5
- [2]Lejeune J Gautier M Turpin R Etude des chromosomes somatiques de neuf enfants mongoliens Comptes Rendus Hebdomadaires des Seances de L'Academie des Sciences 1959 248 1721 1722 13639368
- [27]Lambert MP Diffusable, nonfibrillar ligands derived from Ab1-42 are potent central nervous system neurotoxins PNAS 1998 95 6448 6453 9600986 PMC27787
- [38]Mori C Intraneuronal Abeta42 accumulation in Down syndrome brain Amyloid 2002 9 2 88 102 12440481
- [96]Tamaoka A Amyloid beta protein species in cerebrospinal fluid and in brain from patients with Down's syndrome Ann Neurol 1999 46 6 933 10589550
- [123]Pratico D Down's syndrome is associated with increased 8,12-iso-iPF2alpha-VI levels: evidence for enhanced lipid peroxidation in vivo Ann Neurol 2000 48 5 795 8 11079545
Cited by
Sorted by citations
Diagnosis and Management of Dementia: Review
Arvanitakis, Z., Shah, R. C., & Bennett, D. A. (2019) · JAMA · doi:10.1001/jama.2019.4782 · Cited by 1,561
Wang, C., & Holtzman, D. M. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-019-0478-5 · Cited by 615
Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students
Lepeta, K., Lourenco, M. V., Schweitzer, B. C., Martino Adami, P. V., Banerjee, P., Catuara‐Solarz, S., de La Fuente Revenga, M., Guillem, A. M., Haidar, M., Ijomone, O. M., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13713 · Cited by 386
Telomere Biology and Human Phenotype
Turner, K. J., Vasu, V., & Griffin, D. K. (2019) · Cells · doi:10.3390/cells8010073 · Cited by 415
Dementia in Down syndrome: unique insights for Alzheimer disease research
Lott, I. T., & Head, E. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0132-6 · Cited by 383
Self-citation
Metadata
- Authors
- Head, E., T. Lott, I., M. Wilcock, D., & A. Lemere, C.
- Affiliations
- University of Kentucky (US)
- ORCID
- Head, Elizabeth
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2015-12-07
- Volume
- 13
- Issue
- 1
- Pages
- 18-29
- ISSN
- 1567-2050 (ISSN-L)
- PMC
- PMC4948181
- OpenAlex
- W2190781699
- Cited by
- 289
- References
- 160
- Citations by year
- 2026: 13 · 2025: 30 · 2024: 23 · 2023: 14 · 2022: 18 · 2021: 34 · 2020: 29 · 2019: 29 · 2018: 55 · 2017: 32 · 2016: 10 · 2015: 1
- FWCI
- 35.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG040092, P50AG016573, R01AG16573)
- National Institute of Neurological Disorders and Stroke (NS079637, R01NS079637, R01NS136122)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD065160, R01HD064993)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Down syndrome, Alzheimer's disease, Alzheimer's disease pathology, aging, chromosome 21, amyloid precursor protein, amyloid plaques, neurofibrillary tangles, cerebrovascular pathology, white matter pathology, oxidative damage, neuroinflammation, neuronal loss, dementia onset, brain banks
- MeSH terms
- Neuropathology, Age Factors, Aging, Alzheimer Disease, Animals, Down Syndrome, Humans, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins
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
