9 December 2010. Alzheimer’s disease patients show reduced rates of Aβ clearance, yet normal Aβ production, according to a study posted online in ScienceXpress today. Senior investigator Randall Bateman of Washington University School of Medicine, St. Louis, Missouri, reported these data in July at the International Conference on Alzheimer’s Disease in Honolulu, Hawaii (ARF related conference story).
Using metabolic labeling and other analytical techniques, first author Kwasi Mawuenyega and colleagues measured real-time Aβ turnover in the cerebrospinal fluid of 12 late-onset AD patients and 12 age-matched controls over a 36-hour period. Both groups produced CNS Aβ at similar rates, around 6.8 percent of the total per hour. However, while healthy elderly cleared Aβ40 and Aβ42 at rates of 7.0 and 7.6 percent per hour, respectively, AD patients got rid of their Aβ about 30 percent more slowly. Estimates based on this clearance impairment “suggest that brain Aβ accumulates over approximately 10 years in AD,” the authors wrote.
In addition to impaired CNS Aβ clearance, the AD group had lower concentrations of CSF Aβ42. However, the relationship between these two measures is not fully understood, the authors point out. There may be “more than one pool of Aβ in the CSF, undetected pools of Aβ in CSF by ELISA (e.g., oligomers), or a combined increase in Aβ production with impaired efflux from parenchyma to CSF,” they noted.—Esther Landhuis.
Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, Yarasheski KE, Bateman RJ. Decreased Clearance of CNS Beta-Amyloid in Alzheimer’s Disease. Science. 9 December 2010. Abstract