Biomedical subjects

W R Markesbery

Publications and source records attributed to W R Markesbery.

237 records · Page 14Linked to original sources

PubMedDate not supplied

Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease.

Recent studies have implicated increased oxidative stress in the pathogenesis of Alzheimer's disease (AD). Increased lipid peroxidation and decreased polyunsaturated fatty acid levels have been described in the brain in AD. Four-hydroxynonenal (HNE), an aldehyde product of lipid peroxidation, has been demonstrated to be a neurotoxin in tissue culture and in vivo studies and is elevated in ventricular fluid in AD. We report here an increase in mean free HNE in multiple brain regions in AD compared with age-matched control subjects. These increases reached statistical significance in the amygdala and hippocampus and parahippocampal gyrus, regions showing the most pronounced histopathological alterations in AD. This study, in conjunction with cell culture studies, suggests that HNE may be an important substance in the pathogenesis of neuron degeneration in AD.

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PubMedDate not supplied

Progression of regional neuropathology in Alzheimer disease and normal elderly: findings from the Nun study.

Although diffuse plaques in the neocortex may represent an early stage in the evolution of neuritic plaques, plaques in the striatum and cerebellum retain their predominantly diffuse nature in Alzheimer disease (AD), regardless of disease duration. We had the opportunity to explore the progression of these regional features by using autopsy brain specimens from 15 cognitively normal and five AD subjects, all Catholic sisters enrolled in the Nun Study, a longitudinal study on aging and AD. Neuropathologic changes were assessed in the temporal cortex, striatum, and cerebellum without knowledge of clinical status. We found diffuse plaques in the striatum in six (40%) and cerebellar plaques in none of the brains from the non-demented subjects. Striatal plaques were present in all five and cerebellar plaques in four of the five AD cases. In the 20 cases overall, the presence of striatal plaques generally paralleled the occurrence of neuritic plaques in neocortex and correlated with lower scores on several neuropsychologic tests assessing memory. Our findings suggest that striatal diffuse plaques occur relatively early in the progression of AD pathology and coincide with neocortical pathology and cognitive changes. Thus, it is unlikely that temporal factors alone account for regional differences in progression of AD neuropathology.

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PubMedDate not supplied

Oxidation of cytosolic proteins and expression of creatine kinase BB in frontal lobe in different neurodegenerative disorders.

The presence of the biomarkers of oxidative damage, protein carbonyl formation and the inactivation of oxidatively sensitive brain creatine kinase (CK BB, cytosolic isoform), were studied in frontal lobe autopsy specimens obtained from patients with different age-related neurodegenerative diseases: Alzheimer's disease (AD), Pick's disease (PkD), diffuse Lewy body disease (DLBD), Parkinson's disease (PD), and age-matched control subjects. The CK activity was significantly reduced in the frontal lobe of AD, PkD and DLBD subjects, and CK BB-specific mRNA was significantly reduced in AD and DLBD. Protein carbonyl content was significantly increased in AD, PkD and DLBD. The results of this study confirm that the presence of biomarkers of oxidative damage is related to the presence of histopathological markers of neurodegeneration. Our data suggest that oxidative damage contributes to the development of the symptoms of frontal dysfunction in AD, PkD and DLBD. The development of frontal dysfunction in idiopathic PD might be secondary to oxidative damage and neuronal loss primarily located in the nigrostriatal system. The results of CK BB expression analysis demonstrate that the loss of the isoenzyme in different neurodegenerative diseases is likely the consequence of its posttranslational modification, possibly oxidative damage. Changes in CK BB expression may be an early indicator of oxidative stress in neurons.

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