Abstract
Estrogen exerts beneficial effects on the brain throughout life. Studies demonstrate that estrogen is neuroprotective and that reduced brain estrogen activity may influence the clinical course of Alzheimers disease (AD). Changes in levels of estrogen receptors have been detected in postmortem brain tissue of AD patients. Very little is known about the relationship between clinical stage and levels of estrogen receptors in postmortem brain. We hypothesized that estrogen receptor levels would be related to severity of cognitive impairment assessed proximate to death. Western blotting was used to quantify ER-α and ER-β in nuclear, cytosolic, and crude membrane fractions of superior frontal cortex from 25 AD patients. Multiple linear regression analyses adjusted for age, sex, and education showed a significant linear relationship between Mini-Mental State Examination score (MMSE) and wild-type nuclear ER-α (â = 5.463, p = 0.03), but none between MMSE and wild-type nuclear ER-β (â = 2.29, p = 0.36). We incidentally observed additional higher and lower molecular mass bands for ER-α in study subjects. Additional experiments performed on frontal cortex nuclear fractions prepared from subjects enrolled in a different study confirmed that these same bands are present in female and males with and without AD. Together our data show a relationship between wild-type ER-α and level of cognitive impairment in AD, and also suggest the possibility that variant isoforms of ER-α may be present in frontal cortex of patients with and without AD.
Keywords: Cognition, postmortem brain tissue, dementia, neuroprotection, splice variants, isoforms
Current Alzheimer Research
Title: Levels of Estrogen Receptors α and β in Frontal Cortex of Patients with Alzheimers Disease: Relationship to Mini-Mental State Examination Scores
Volume: 5 Issue: 1
Author(s): Jeremiah F. Kelly, Julia L. Bienias, Avni Shah, Kathleen A. Meeke, Julie A. Schneider, Edwin Soriano and David A. Bennett
Affiliation:
Keywords: Cognition, postmortem brain tissue, dementia, neuroprotection, splice variants, isoforms
Abstract: Estrogen exerts beneficial effects on the brain throughout life. Studies demonstrate that estrogen is neuroprotective and that reduced brain estrogen activity may influence the clinical course of Alzheimers disease (AD). Changes in levels of estrogen receptors have been detected in postmortem brain tissue of AD patients. Very little is known about the relationship between clinical stage and levels of estrogen receptors in postmortem brain. We hypothesized that estrogen receptor levels would be related to severity of cognitive impairment assessed proximate to death. Western blotting was used to quantify ER-α and ER-β in nuclear, cytosolic, and crude membrane fractions of superior frontal cortex from 25 AD patients. Multiple linear regression analyses adjusted for age, sex, and education showed a significant linear relationship between Mini-Mental State Examination score (MMSE) and wild-type nuclear ER-α (â = 5.463, p = 0.03), but none between MMSE and wild-type nuclear ER-β (â = 2.29, p = 0.36). We incidentally observed additional higher and lower molecular mass bands for ER-α in study subjects. Additional experiments performed on frontal cortex nuclear fractions prepared from subjects enrolled in a different study confirmed that these same bands are present in female and males with and without AD. Together our data show a relationship between wild-type ER-α and level of cognitive impairment in AD, and also suggest the possibility that variant isoforms of ER-α may be present in frontal cortex of patients with and without AD.
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Cite this article as:
Kelly F. Jeremiah, Bienias L. Julia, Shah Avni, Meeke A. Kathleen, Schneider A. Julie, Soriano Edwin and Bennett A. David, Levels of Estrogen Receptors α and β in Frontal Cortex of Patients with Alzheimers Disease: Relationship to Mini-Mental State Examination Scores, Current Alzheimer Research 2008; 5 (1) . https://dx.doi.org/10.2174/156720508783884611
DOI https://dx.doi.org/10.2174/156720508783884611 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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