Elevated plasma beta-amyloid peptide Abeta(42) levels, incident dementia, and mortality in Down syndrome

Topic: Brain proteins, microglia and lab models

Background Deposition of the beta-amyloid peptide Abeta(42) is thought to be an important initial step in the pathogenesis of Alzheimer disease (AD). Individuals with Down syndrome have increased levels of beta-amyloid peptides and an increased risk for AD. Objective To examine the relation of plasma levels of Abeta(42) and Abeta(40) to the risk of dementia in nondemented participants and all-cause mortality in adults with Down syndrome. Design Prospective, community-based longitudinal cohort study. Setting State and voluntary service providers in New York State. Participants Adults with Down syndrome (N = 204). Main outcome measure Plasma Abeta(42) and Abeta(40) levels were measured at initial examination. Participants were assessed for cognitive and functional abilities, behavioral/psychiatric conditions, and health and vital status at 14- to 18-month intervals for 4 cycles of data collection. Results Among participants who were nondemented at baseline, those in the middle and highest tertiles of plasma Abeta(42) levels were more than 2 times as likely to develop AD as those in the lowest tertile. Compared with participants without AD, participants with prevalent AD had higher levels of plasma Abeta(42) but not Abeta(40). Among all participants, those in the highest tertile of plasma Abeta(42) level at baseline were more than twice as likely to die during the study period as those in the lowest tertile, whereas there was no difference in risk of death between those in the middle and lowest tertiles of plasma Abeta(42) level. Conclusion Elevations in plasma Abeta(42) peptide levels are associated with earlier onset of AD and increased risk of death.

Key findings

• Individuals with Down syndrome have increased levels of beta-amyloid peptides and an increased risk for AD.
• Results Among participants who were nondemented at baseline, those in the middle and highest tertiles of plasma Abeta(42) levels were more than 2 times as likely to develop AD as those in the lowest tertile.
• Compared with participants without AD, participants with prevalent AD had higher levels of plasma Abeta(42) but not Abeta(40).
• Conclusion Elevations in plasma Abeta(42) peptide levels are associated with earlier onset of AD and increased risk of death.

Why it matters

In 204 adults with Down syndrome followed over time, those who were not demented at the start and had middle or highest levels of plasma Abeta(42) were more than twice as likely to develop Alzheimer's disease as those with the lowest levels. Among all participants, those in the highest tertile of plasma Abeta(42) at baseline were more than twice as likely to die during the study period.

Study details

• Study designcohort study
• Participants204
• Evidence strengthModerate

Read the original

• DOI: 10.1001/archneur.64.7.1007
• PubMed: 17620492
• Original source →
• Free full text: PubMed Central →

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

@article{schupf2007-17620492,
  author  = {Schupf, N. and Patel, B. and Pang, D. and Zigman, W. B. and Silverman, W. and Mehta, P. D. and Mayeux, R.},
  title   = {{Elevated plasma beta-amyloid peptide Abeta(42) levels, incident dementia, and mortality in Down syndrome}},
  journal = {Archives of neurology},
  year    = {2007},
  doi     = {10.1001/archneur.64.7.1007},
  pmid    = {17620492},
  url     = {https://doi.org/10.1001/archneur.64.7.1007}
}

Studies this one cites

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

• Plasma Abeta(1-40) and Abeta(1-42) and the risk of dementia: a prospective case-cohort study The Lancet. Neurology · 2006-08-01 · usefulness score 67/100 · How common it is
• CSF markers for incipient Alzheimer's disease The Lancet. Neurology · 2003-10-01 · usefulness score 57/100 · Getting a diagnosis
• Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease Archives of neurology · 2000-01-01 · usefulness score 55/100 · Getting a diagnosis
• Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. Journal of Lipid Research · 1990-03-01 · usefulness score 53/100 · Genetics
• A prospective study of Alzheimer disease in Down syndrome Archives of neurology · 1989-08-01 · usefulness score 49/100 · How common it is

Later studies that cite this one

10 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.

• Plasma and CSF biomarkers for the diagnosis of Alzheimer's disease in adults with Down syndrome: a cross-sectional study The Lancet. Neurology · 2018-08-29 · usefulness score 64/100 · Biomarkers
• Towards onset prevention of cognition decline in adults with Down syndrome (The TOP-COG study): A pilot randomised controlled trial Trials · 2016-07-29 · usefulness score 60/100 · Down syndrome and Alzheimer's
• Alzheimer's disease associated with Down syndrome: a genetic form of dementia The Lancet. Neurology · 2021-11-01 · usefulness score 59/100 · Prevention and risk
• Toward onset prevention of cognitive decline in adults with Down syndrome (the TOP-COG study): study protocol for a randomized controlled trial Trials · 2014-06-03 · usefulness score 57/100 · Treatments
• The effects of mosaicism on biological and clinical markers of Alzheimer's disease in adults with Down syndrome EBioMedicine · 2024-11-04 · usefulness score 56/100 · Down syndrome and Alzheimer's
• Change in plasma Aß peptides and onset of dementia in adults with Down syndrome Neurology · 2010-11-01 · usefulness score 54/100 · Down syndrome and Alzheimer's
• Dementia in Down's syndrome The Lancet. Neurology · 2016-04-11 · usefulness score 51/100 · Brain tissue and pathology
• Plasma Aβ42 and Total Tau Predict Cognitive Decline in Amnestic Mild Cognitive Impairment Scientific reports · 2019-09-27 · usefulness score 47/100 · Tau biomarkers

Related studies in Down syndrome and Alzheimer's

• Plasma amyloid beta protein 1-42 levels are increased in old Down Syndrome but not in young Down Syndrome Neuroscience letters · 2003-05-01 · usefulness score 36/100
• Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome Neuroscience letters · 2002-06-01 · usefulness score 38/100
• Truncated beta-amyloid peptide channels provide an alternative mechanism for Alzheimer's Disease and Down syndrome Proceedings of the National Academy of Sciences of the United States of America · 2010-03-22 · usefulness score 36/100
• Increased amyloid beta protein levels in children and adolescents with Down syndrome Journal of the neurological sciences · 2007-02-02 · usefulness score 42/100
• Amyloid beta protein (Abeta) deposition in chromosome 14-linked Alzheimer's disease: predominance of Abeta42(43) Annals of neurology · 1996-08-01 · usefulness score 40/100
• Molecular genetics of Alzheimer's disease and the amyloid beta peptide precursor gene Annals of medicine · 1989-01-01 · usefulness score 36/100

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.

• Down syndrome and Alzheimer disease Progress in clinical and biological research · 1992-01-01 · usefulness score 33/100 · Down syndrome and Alzheimer's
• Down syndrome: molecular mapping of the congenital heart disease and duodenal stenosis American journal of human genetics · 1992-02-01 · usefulness score 40/100 · Down syndrome and Alzheimer's
• Health care concerns and guidelines for adults with Down syndrome American journal of medical genetics · 1999-06-01 · usefulness score 41/100 · Down syndrome and Alzheimer's

Similar studies

• Quantification of modified amyloid beta peptides in Alzheimer disease and Down syndrome brains 1998 · Down syndrome and Alzheimer's
• Cerebrovascular disease drives Alzheimer plasma biomarker concentrations in adults with Down syndrome 2023 · Down syndrome and Alzheimer's
• Alzheimer-Like Pattern of Hypometabolism Emerges with Elevated Amyloid-β Burden in Down Syndrome 2018 · Down syndrome and Alzheimer's
• Characteristic developmental expression of amyloid beta40, 42 and 43 in patients with Down syndrome 2003 · Down syndrome and Alzheimer's
• Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy, including trisomy 21: requirement for tau and APP 2010 · Down syndrome and Alzheimer's
• Beta-amyloid, oxidative stress and down syndrome 2006 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground A modified beta-amyloid hypothesis: intraneuronal accumulation of the beta-amyloid peptide--the first step of a fatal cascade Journal of neurochemistry · 2004-11-01 · usefulness score 36/100
• Newest in this subject Differential endothelial cell remodeling in Down syndrome and APP duplication drives distinct blood brain barrier dysfunction bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Memory and Plasma pTau217 Refine Prognosis in Down Syndrome Annals of neurology · 2026-10-02 · Peer-reviewed · usefulness score 47/100

See all studies in Down syndrome and Alzheimer's →