Posted 14 July 2005
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Biomarkers of Alzheimer's disease: F2-isoprostanes
By Domenico Pratico
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Background: AD is the most common, complex, and challenging neurodegenerative disease associated with dementia in the elderly. Besides the pathological hallmarks of the disease, which include senile plaques and neurofibrillary tangles, AD brain exhibits evidence of reactive oxygen species (ROS)-mediated damage. Since the brain has very high lipid content and in particular high levels of polyunsaturated fatty acids (PUFA), which are easily susceptible to ROS attack, this damage will manifest predominantly as lipid peroxidation. F2-isoprostanes (F2-iPs) are members of a complex family of lipids produced in vivo by ROS-catalyzed peroxidation of PUFA. Objective(s): Consistent data in the literature have shown that F2-iP levels are increased in post-mortem brain tissue and ventricular CSF, as well as intra-vitam lumbar CSF of AD patients. Methods: Gas/chromatography/mass spectrometry assay Results: This marker of oxidative stress is highly specific for AD, since it is not increased in other neurodegenerative disorders such as Parkinson's disease (PD) or Fronto-temporal dementia (FTD). We have shown that a specific F2-iP isomer, 8,12-iso-iPF2a-VI, is also elevated in patients with clinical diagnosis of mild cognitive impairment (MCI), a syndrome that often precedes AD, and in young Down's subjects. Interestingly, we found that MCI subjects were different from elderly controls with respect only to this and not other CSF markers (i.e. tau or Ab). Finally, in a longitudinal study with MCI patients we found that compared with CSF tau and Ab, only the 8,12-iso-iPF2a-VI levels showed a significant and progressive elevation. Conclusions: These data support the use of this F2-iP as an AD biomarker for clinical and pre-clinical diagnosis, it also can help patients selection and rationale for dose-selection of therapeutics with anti-oxidant activity in this disease.
Citation: Pratico, D. Biomarkers of Alzheimer's disease: F2-isoprostanes. NeuroBiology of Aging, Volume 25, Number S2 , July 2004, Page 5
View Domenico Pratico's presentation.
Note: Audio for this presentation is unavailable.
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