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Sarah Scott

Publications and source records attributed to Sarah Scott.

3 recordsLinked to original sources
PubMed2003

Thiorphan-induced neprilysin inhibition raises amyloid beta levels in rabbit cortex and cerebrospinal fluid.

Studies on the pathogenesis of Alzheimer's disease (AD) suggest overproduction of amyloid beta (Abeta) may not be the only pathogenic route to AD. Decreased degradation of Abeta is another possible disease mechanism. Neprilysin is a neutral endopeptidase that has been proposed to be the major enzyme responsible for Abeta degradation. Studies have reported correlations between Abeta deposition and neprilysin activity in the human brain. This study shows that intracerebroventricular infusion of thiorphan, a neprilysin inhibitor, raises cortical and cerebrospinal fluid (CSF) Abeta concentrations in rabbits. Rabbits treated with thiorphan for 5 days had levels of CSF and cortical Abeta40 that were 147 and 142% of the control group, respectively. Results for Abeta42 showed a similar trend. The results indicate that age-related decreases of neprilysin could lead to increased brain concentrations of Abeta, plaque formation, and AD.

Alzheimer Disease↗
PubMed2003

Hippocampal sclerosis dementia with tauopathy.

In some elderly individuals with dementia, hippocampal sclerosis (HS) is the only remarkable autopsy finding. The cause of HS in this setting is puzzling, since known causes of HS such as seizures or global hypoxic-ischemic episodes are rarely present. We here describe a series of HS cases that have a widespread neuronal and/or glial tauopathy. Of 14 consecutive cases of HS, 12 had been clinically diagnosed with dementia and/or Alzheimer's disease (AD) while 2 were non-demented; 7 cases had also been clinically diagnosed with parkinsonism. In addition to HS, 6 cases also met pathologic diagnostic criteria for AD. Gallyas silver staining and immunohistochemistry with the AT8 antibody revealed a glial and/or neuronal tauopathy in 12 of 14 cases, with frequent positive neurons and/or glial cells in the neocortex, basal ganglia, thalamus and/or limbic regions; in addition, 8 of the 14 cases had argyrophilic grains. Screening for known tau mutations was negative in all cases. Western blots of sarkosyl-insoluble tau protein showed a mixture of 3- and 4-repeat forms. The results suggest that most cases of HS dementia are sporadic multisystem tauopathies; we suggest the term "hippocampal sclerosis dementia with tauopathy" (HSDT) for these.

Aged↗