Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis

Donna M. Wilcock, W. Sue T. Griffin

Research output: Contribution to journalReview articlepeer-review

161 Scopus citations

Abstract

Down syndrome (DS) is the result of triplication of chromosome 21 (trisomy 21) and is the prevailing cause of mental retardation. In addition to the mental deficiencies and physical anomalies noted at birth, triplication of chromosome 21 gene products results in the neuropathological and cognitive changes of Alzheimer's disease (AD). Mapping of the gene that encodes the precursor protein (APP) of the β-amyloid (Aβ) present in the Aβ plaques in both AD and DS to chromosome 21 was strong evidence that this chromosome 21 gene product was a principal neuropathogenic culprit in AD as well as DS. The discovery of neuroinflammatory changes, including dramatic proliferation of activated glia overexpressing a chromosome 2 gene product - the pluripotent immune cytokine interleukin-1 (IL-1) - and a chromosome 21 gene product - S100B - in the brains of fetuses, neonates, and children with DS opened the possibility that early events in Alzheimer pathogenesis were driven by cytokines. The specific chromosome 21 gene products and the complexity of the mechanisms they engender that give rise to the neuroinflammatory responses noted in fetal development of the DS brain and their potential as accelerators of Alzheimer neuropathogenesis in DS are topics of this review, particularly as they relate to development and propagation of neuroinflammation, the consequences of which are recognized clinically and neuropathologically as Alzheimer's disease.

Original languageEnglish
Article number864
JournalJournal of Neuroinflammation
Volume10
DOIs
StatePublished - Jul 16 2013

Bibliographical note

Funding Information:
The authors thank Dr. Orwa Aboud for critical review of the manuscript. WSTG supported in part by NIH/NIA AG12411 and the Windgate Foundation. DMW supported in part by NS079637 and P20GM103486.

ASJC Scopus subject areas

  • Neuroscience (all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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