Association between Inflammatory Conditions and Alzheimer's Disease Age of Onset in Down Syndrome

Topic: Amyloid, tau and blood-test diagnosis

Adults with Down syndrome (DS) have an exceptionally high prevalence of Alzheimer disease (AD), with an earlier age of onset compared with the neurotypical population. In addition to beta amyloid, immunological processes involved in neuroinflammation and in peripheral inflammatory/autoimmune conditions are thought to play important roles in the pathophysiology of AD. Individuals with DS also have a high prevalence of autoimmune/inflammatory conditions which may contribute to an increased risk of early AD onset, but this has not been studied. Given the wide range in the age of AD onset in those with DS, we sought to evaluate the relationship between the presence of inflammatory conditions and the age of AD onset. We performed a retrospective study on 339 adults with DS, 125 who were cognitively stable (CS) and 214 with a diagnosis of AD. Data were available for six autoimmune conditions (alopecia, celiac disease, hypothyroidism, psoriasis, diabetes and vitamin B12 deficiency) and for one inflammatory condition, gout. Gout was associated with a significant delay in the age of AD onset by more than 2.5 years. Our data suggests that inflammatory conditions may play a role in the age of AD onset in DS. Further studies are warranted.

Key findings

• Adults with Down syndrome (DS) have an exceptionally high prevalence of Alzheimer disease (AD), with an earlier age of onset compared with the neurotypical population.
• Individuals with DS also have a high prevalence of autoimmune/inflammatory conditions which may contribute to an increased risk of early AD onset, but this has not been studied.
• Gout was associated with a significant delay in the age of AD onset by more than 2.5 years.
• Our data suggests that inflammatory conditions may play a role in the age of AD onset in DS.

Why it matters

In a retrospective study of 339 adults with Down syndrome, gout was associated with a delay of more than 2.5 years in the age at which Alzheimer's disease began. This is an observed association, not a demonstrated treatment or prevention, and the authors call for further studies.

Study details

• Participants339
• Evidence strengthLow

Read the original

• DOI: 10.3390/jcm10143116
• PubMed: 34300282
• Original source →
• Free full text: Journal of Clinical Medicine →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{lai2021-34300282,
  author  = {Lai, F. and Mercaldo, N. and Wang, C. M. and Hersch, G. G. and Rosas, H. D.},
  title   = {{Association between Inflammatory Conditions and Alzheimer's Disease Age of Onset in Down Syndrome}},
  journal = {Journal of clinical medicine},
  year    = {2021},
  doi     = {10.3390/jcm10143116},
  pmid    = {34300282},
  url     = {https://doi.org/10.3390/jcm10143116}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Risk of dementia in diabetes mellitus: a systematic review The Lancet. Neurology · 2006-01-01 · usefulness score 73/100 · How common it is
• Neuroinflammation in Alzheimer's disease The Lancet Neurology · 2015-03-16 · usefulness score 64/100 · Inflammation and the immune system
• Alzheimer's Disease: The Amyloid Cascade Hypothesis Science · 1992-04-10 · usefulness score 61/100 · Disease mechanisms
• The natural history of dementia in Down's syndrome Archives of neurology · 1990-03-01 · usefulness score 57/100 · Digital health tools
• Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome Annals of Neurology · 1985-03-01 · usefulness score 56/100 · Down syndrome and Alzheimer's
• Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight Nature reviews. Immunology · 2018-12-01 · usefulness score 54/100 · Genetics
• A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome Journal of intellectual disability research : JIDR · 2017-06-29 · usefulness score 53/100 · Brain tissue and pathology
• A prospective study of Alzheimer disease in Down syndrome Archives of neurology · 1989-08-01 · usefulness score 49/100 · How common it is
• Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis Journal of neuroinflammation · 2013-07-16 · usefulness score 47/100 · Down syndrome and Alzheimer's
• Superoxide dismutase SOD1, encoded on chromosome 21, but not SOD2 is overexpressed in brains of patients with Down syndrome Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2001-01-01 · usefulness score 40/100 · Down syndrome and Alzheimer's

Later studies that cite this one

1 study in the alzhub library lists this one in its references.

• Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer's disease: a cross-sectional study The Lancet. Neurology · 2023-01-01 · usefulness score 60/100 · Biomarkers

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• Executive function in adolescents with Down Syndrome Journal of intellectual disability research : JIDR · 2010-02-28 · usefulness score 41/100 · Down syndrome and Alzheimer's
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