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Genetic and host factors for dementia in Down's syndrome

  • Nicole Schupf (a1)
Abstract
Background

The high risk for dementia in adults with Down's syndrome has been attributed to triplication and overexpression of the gene for amyloid precursor protein (APP). But the wide variation in age at onset must be due to other risk factors.

Aims

To identify factors which influence age at onset of dementia in Down's syndrome.

Method

Studies of factors which influence formation of beta-amyloid (Aβ) were reviewed, including atypical karyotypes, susceptibility genotypes, gender and oestrogen deficiency, and individual differences in Aβ peptide levels.

Results

The apolipoprotein E $4 allele, oestrogen deficiency and high levels of Aβl-42 peptide are associated with earlier onset of dementia, while atypical karyotypes and the apolipoprotein E $2 allele are associated with reduced mortality and reduced risk of dementia.

Conclusions

Factors which influence Aβ levels, rather than overexpression of APP, may account for the differences in age at onset of dementia in Down's syndrome.

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Copyright
Corresponding author
Nicole Schupf, Ph D, New York State Institute for Basic Research, 1050 Forest Hill Road, Staten Island, NY 10314. Tel: 001 718 494 5301; Fax: 001 718 494 5395; e-mail: ns24@columbia.edu
Footnotes
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Presented in part as the Blake Marsh Lecture at the Annual Meeting of the Royal College of Psychiatrists, 6 July 2000, Edinburgh.

Declaration of interest

Grants IIRG-90-067 and RG3-96-077 from the Alzheimer's Association, Federal grants AG14673, HD35897, P50AG08702 and funds from New York State through its Office of Mental Retardation and Developmental Disabilities.

Footnotes
References
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Genetic and host factors for dementia in Down's syndrome

  • Nicole Schupf (a1)
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