Differential Associations of Apolipoprotein E ε4 Genotype With Attentional Abilities Across the Life Span of Individuals With Down Syndrome

Topic: Brain proteins, microglia and lab models

The ε4 allele of the apolipoprotein E gene (APOE ε4) is associated with an additional risk for AD. In typical development, there is evidence that the APOE ε4 genotype is associated with an early cognitive advantage. Results The child sample comprised 23 ε4 carriers and 57 ε4 noncarriers. For the children, a significant difference between trajectory intercepts (ηp2 = 0.14) indicated that ε4 carriers (B = 100.24 [95% CI, 18.52-181.96]) exhibited an attentional advantage over ε4 noncarriers (B = 314.78 [95% CI, 252.17-377.39]). Conclusions and relevance APOE ε4 is associated with an attentional advantage early in development and a disadvantage later in life for individuals with DS, similar to the pattern reported in typical development.

@article{dsouza2020-32986108,
  author  = {D'Souza, H. and Mason, L. and Mok, K. Y. and Startin, C. M. and Hamburg, S. and Hithersay, R. and Baksh, R. A. and Hardy, J. and others},
  title   = {{Differential Associations of Apolipoprotein E ε4 Genotype With Attentional Abilities Across the Life Span of Individuals With Down Syndrome}},
  journal = {JAMA network open},
  year    = {2020},
  doi     = {10.1001/jamanetworkopen.2020.18221},
  pmid    = {32986108},
  url     = {https://doi.org/10.1001/jamanetworkopen.2020.18221}
}

Key findings

• The ε4 allele of the apolipoprotein E gene (APOE ε4) is associated with an additional risk for AD.
• In typical development, there is evidence that the APOE ε4 genotype is associated with an early cognitive advantage.
• Results The child sample comprised 23 ε4 carriers and 57 ε4 noncarriers.
• For the children, a significant difference between trajectory intercepts (ηp2 = 0.14) indicated that ε4 carriers (B = 100.24 [95% CI, 18.52-181.96]) exhibited an attentional advantage over ε4 noncarriers (B = 314.78 [95% CI, 252.17-377.39]).
• Conclusions and relevance APOE ε4 is associated with an attentional advantage early in development and a disadvantage later in life for individuals with DS, similar to the pattern reported in typical development.

Why it matters

In children with Down syndrome, this study found that APOE ε4 carriers showed an attentional advantage over noncarriers, while the authors note ε4 is linked to a disadvantage later in life. It is a cross-sectional study and does not test any treatment, cure, or prevention.

Study details

• Study designcross-sectional
• Participants240
• Evidence strengthLow

Read the original

• DOI: 10.1001/jamanetworkopen.2020.18221
• PubMed: 32986108
• Original source →
• Free full text: JAMA Network Open →

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.

• The effect of APOE and other common genetic variants on the onset of Alzheimer's disease and dementia: a community-based cohort study The Lancet. Neurology · 2018-03-16 · usefulness score 70/100 · Long-term cohort studies
• Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers Dementia (Basel, Switzerland) · 1994-09-01 · usefulness score 55/100 · Cognitive tests and assessment
• Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study JAMA neurology · 2014-01-01 · usefulness score 55/100 · Genetics
• A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome Nature reviews. Neuroscience · 2015-08-05 · usefulness score 52/100 · Risk factors

Related studies in Down syndrome and Alzheimer's

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• Relation between apolipoprotein E genotype, hepatitis B virus status, and thyroid status in a sample of older persons with Down syndrome American journal of medical genetics. Part A · 2003-07-01 · usefulness score 40/100
• [The apolipoprotein E genotype and Down's syndrome] Revista clinica espanola · 1997-10-01 · usefulness score 27/100
• Balance and Gait: Associations With Cognitive Impairment and Dementia in Individuals With Down Syndrome Alzheimer disease and associated disorders · 2023-10-02 · usefulness score 39/100
• Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome-Alzheimer’s disease Acta neuropathologica · 2025-02-25 · usefulness score 47/100
• Evolution of neuroinflammation across the lifespan of individuals with Down syndrome Brain : a journal of neurology · 2020-12-01 · usefulness score 48/100

Also tagged “down”

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• Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years JAMA neurology · 2019-02-01 · usefulness score 70/100 · Genetics
• Cerebral extracellular preamyloid deposits in Alzheimer's disease, Down syndrome and nondemented elderly individuals Progress in clinical and biological research · 1989-01-01 · usefulness score 27/100 · Down syndrome and Alzheimer's
• The mouse homolog of the human amyloid beta protein (AD-AP) gene is located on the distal end of mouse chromosome 16: further extension of the homology between human chromosome 21 and mouse chromosome 16 Biochemical and biophysical research communications · 1987-04-01 · usefulness score 40/100 · Down syndrome and Alzheimer's

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• Association of a wide range of chronic diseases and apolipoprotein E4 genotype with subsequent risk of dementia in community-dwelling adults: A retrospective cohort study 2022 · Long-term cohort studies

More on Down syndrome and Alzheimer's

• A review that covers this ground New therapies for treating Down syndrome require quality of life measurement American journal of medical genetics. Part A · 2013-03-12 · usefulness score 33/100
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