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Papassotiropoulos, A. et al.

Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia. It is characterized by beta-amyloid (A beta) plaques, neurofibrillary tangles and the degeneration of specifically vulnerable brain neurons. We observed high expression of the cholesterol 25-hydroxylase (CH25H) gene in specifically vulnerable brain regions of AD patients. CH25H maps to a region within 10q23 that has been previously linked to sporadic AD. Sequencing of the 5' region of CH25H revealed three common haplotypes, CH25Hchi2, CH25Hchi3 and CH25Hchi4; CSF levels of the cholesterol precursor lathosterol were higher in carriers of the CH25Hchi4 haplotype. In 1,282 patients with AD and 1,312 healthy control subjects from five independent populations, a common variation in the vicinity of CH25H was significantly associated with the risk for sporadic AD (p = 0.006). Quantitative neuropathology of brains from elderly non-demented subjects showed brain A beta deposits in carriers of CH25Hchi4 and CH25Hchi3 haplotypes, whereas no A beta deposits were present in CH25Hchi2 carriers. Together, these results are compatible with a role of CH25Hchi4 as a putative susceptibility factor for sporadic AD; they may explain part of the linkage of chromosome 10 markers with sporadic AD, and they suggest the possibility that CH25H polymorphisms are associated with different rates of brain A beta deposition.[1]

References

Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's disease. Papassotiropoulos, A., Lambert, J.C., Wavrant-De Vrièze, F., Wollmer, M.A., von der Kammer, H., Streffer, J.R., Maddalena, A., Huynh, K.D., Wolleb, S., Lutjohann, D., Schneider, B., Thal, D.R., Grimaldi, L.M., Tsolaki, M., Kapaki, E., Ravid, R., Konietzko, U., Hegi, T., Pasch, T., Jung, H., Braak, H., Amouyel, P., Rogaev, E.I., Hardy, J., Hock, C., Nitsch, R.M. Neuro-degenerative diseases. (2005) [Pubmed]

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