title: Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis.
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.
authors.affiliation: Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Wilcock
authors.forename: W Sue T
authors.initials: WS
authors.lastname: Griffin
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology*