Monday, January 18, 2010

Alzheimer's Disease & Down Syndrome: Linked?

There has been talk on some of the Down syndrome lists about new research which came out recently about Alzheimer's disease. They found that there is a sort of mosaicism found in patients with AD - a third 21st chromosome in some of their cells. Which may be responsible for all the extra amyloid plaques which are a large part of AD.

Are Down syndrome & Alzheimer's disease linked more closely than we realized? That is what it appears.

Alzheimer A{beta} Peptide Induces Chromosome Mis-Segregation and Aneuploidy, Including Trisomy 21; Requirement for Tau and APP.

Granic A, Padmanabhan J, Norden M, Potter H.

Eric Pfeiffer Suncoast Alzheimer's Center, Byrd Alzheimer's Institute, Florida Alzheimer's Disease Research Center, Department of Molecular Medicine, College of Medicine, School of Aging Studies, College of Behavioral and Community Sciences, University of South Florida, Tampa FL, 33613.

Monitoring Editor: Yixian Zheng Both sporadic and familial Alzheimer's disease patients exhibit increased chromosome aneuploidy, particularly trisomy 21, in neurons and other cells. Significantly, trisomy 21/Down syndrome patients develop early onset AD pathology. We investigated the mechanism underlying mosaic chromosome aneuploidy in AD and report that FAD mutations in the Alzheimer Amyloid Precursor Protein gene, APP, induce chromosome mis-segregation and aneuploidy in transgenic mice and in transfected cells. Furthermore, adding synthetic Abeta peptide, the pathogenic product of APP, to cultured cells causes rapid and robust chromosome mis-segregation leading to aneuploid, including trisomy 21, daughters, which is prevented by LiCl addition or Ca++ chelation and is replicated in tau KO cells, implicating GSK-3beta, calpain, and Tau-dependent microtubule transport in the aneugenic activity of Abeta. Furthermore, APP KO cells are resistant to the aneugenic activity of Abeta, as they have been shown previously to be resistant to Abeta-induced tau phosphorylation and cell toxicity. These results indicate that Abeta-induced microtubule dysfunction leads to aneuploid neurons and may thereby contribute to the pathogenesis of Alzheimer's disease.

**Full Text:

Quote from the full text:

"In sum, the data of this paper and previous results show that the AB peptide found at increased levels in both sporadic and familial Alzheimer's disease interferes with mitosis and chromosome segregation, thus leading to trisomy 21 mosaicism and other chromosome aneuploidy. The implication of the results is that MT disruption leading to cell cycle, chromosome mis-segregation, and other cytoskeletal defects in neuronal precursor cells may underlie many of the neurotoxic aspects of Alzheimer's disease. The findings also suggests that novel approaches to diagnosis and treatment directed at detecting and preventing disruption of MT function and/or the development of chromosome aneuploidy with age may be successful against Alzheimer's disease and possibly other age associated disorders."

This is one main reason Longvida Curcumin has captured so much attention in the Down syndrome community. It is an excellent antioxidant, but it has the potential to clear those nasty amyloid plaques from the brain. That shows much promise!



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