dinoprost and Dementia

To determine the utility of 8,12-isoprostaneF2alpha-VI (iP), a specific and sensitive index of lipid peroxidation, as a biomarker for dementia in Parkinson disease (PD).. iP is a member of the F2-isoprostanes family that has been shown to be promising biomarker for Alzheimer disease. However, iP levels have not been studied in patients with clinical diagnosis of PD or Parkinson disease with dementia (PDD).. PD and PDD patient plasma and urine iP levels were compared with age-matched and sex-matched controls. Clinical measures including demographics and tests of motor function, affect, and cognition were assessed and compared with iP levels.. There were no differences in plasma iP levels between PD subjects and controls (299 vs. 306 pg/mL; P=0.6). Urine iP levels were higher in cases than controls (2.8 vs. 2.1 ng/mg Cr; P=0.003), but levels were lower than those seen in Alzheimer disease patients in prior studies. Within PD subjects, there was no association of iP levels in either the plasma or urine with performance on any clinical measure.. Plasma and urine iP levels do not seem to be substantially elevated in PD and are not associated with severity of cognitive impairment in PDD.

Topics: Aged; Aged, 80 and over; Biomarkers; Cognition Disorders; Dementia; Dinoprost; Disability Evaluation; Female; Humans; Lipid Peroxidation; Male; Mental Status Schedule; Middle Aged; Parkinson Disease; Prognosis; Reference Values

Guam parkinsonism-dementia complex (PDC) is a neurodegenerative tauopathy in ethnic Chamorro residents of the Mariana Islands that manifests clinically with parkinsonism as well as dementia and is characterized neuropathologically by prominent cortical neuron loss in association with extensive telencephalic neurofibrillary tau pathology. To further characterize cortical gray and white matter tau, alpha-synuclein and lipid peroxidation pathologies in Guam PDC, we examined the brains of 17 Chamorro PDC and control subjects using biochemical and immunohistological techniques. We observed insoluble tau pathology in both gray and white matter of PDC and Guam control cases, with frontal and temporal lobes being most severely affected. Using phosphorylation dependent anti-tau antibodies, abundant tau inclusions were detected by immunohistochemistry in both neuronal and glial cells of the neocortex, while less alpha-synuclein pathology was observed in more limited brain regions. Further, in sharp contrast to Alzheimer's disease (AD), levels of the lipid peroxidation product 8, 12-iso-iPF(2alpha)-VI isoprostane were not elevated in Guam PDC brains relative to controls. Thus, although the tau pathologies of Guam PDC share similarities with AD, the composite Guam PDC neuropathology profile of tau, alpha-synuclein and 8, 12-iso-iPF(2alpha)-VI isoprostane reported here more closely resembles that seen in other tauopathies including frontotemporal dementias (FTDs), which may imply that Guam PDC and FTD tauopathies share underlying mechanisms of neurodegeneration.

Topics: Aged; Aged, 80 and over; alpha-Synuclein; Dementia; Dinoprost; Female; Gene Expression Regulation; Guam; Humans; Lipid Peroxidation; Male; Middle Aged; Native Hawaiian or Other Pacific Islander; Neurons; Parkinson Disease; Periaqueductal Gray; tau Proteins

Topics: Alzheimer Disease; Biomarkers; Brain Chemistry; Dementia; Dinoprost; Humans; Lipid Peroxidation; Oxidative Stress

To quantify the isoprostane 8,12-iso-iPF2alpha-VI in brain tissues obtained from patients with AD, patients with frontotemporal dementia (FTD), and controls.. Enhanced brain oxidative stress with secondary damage to cellular macromolecules may play a role in the pathogenesis of AD and FTD. The isoprostane 8,12-iso-iPF2alpha-VI is a specific and sensitive marker of in vivo lipid peroxidation and is increased in AD.. Levels of this isoprostane were determined by gas chromatography/negative ion chemical ionization mass spectrometry.. Levels of 8,12-iso-iPF2alpha-VI were markedly elevated in both frontal and temporal cortex of AD brains compared to the corresponding areas of FTD and controls. No significant difference in brain 8,12-iso-iPF2alpha-VI levels for any regions considered was observed between FTD and controls.. Lipid peroxidation is a feature of AD, but not FTD. The generation of 8,12-iso-iPF(2alpha)-VI in the brain is not a general or final common pathway of neurodegeneration, but may be relatively specific for disease processes in AD and not FTD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Brain Chemistry; Dementia; Dinoprost; Female; Gas Chromatography-Mass Spectrometry; Humans; Lipid Peroxidation; Male; Middle Aged; Nerve Degeneration; Oxidative Stress; Parkinson Disease; Pick Disease of the Brain; Supranuclear Palsy, Progressive