Estrogen Therapy for Prevention of Alzheimer’s Disease But Not for Rehabilitation Following Onset of Disease: The Healthy Cell Bias of Estrogen Action

2005 ◽  
pp. 153-180
Endocrinology ◽  
2005 ◽  
Vol 146 (6) ◽  
pp. 2774-2781 ◽  
Author(s):  
Pattie S. Green ◽  
Kelly Bales ◽  
Steven Paul ◽  
Guojun Bu

Abstract Epidemiological studies implicate estrogen deprivation as a risk factor for Alzheimer’s disease and postmenopausal estrogen replacement as protective factor. One potential mechanism involves estrogen attenuation of β-amyloid (Aβ) peptide accumulation. We examined the effect of estrogen on amyloid accumulation in female PDAPP mice, which express human amyloid precursor protein (APP) with the V717F mutation. These animals deposit Aβ 1–42 in the hippocampus and neocortex and develop Alzheimer-like neuropathology. Mice were subjected to ovariectomy, ovariectomy with estrogen replacement, or sham surgery at 3 months of age, and levels of cerebral Aβ 1–40 and 1–42 were determined after 5 months of treatment. Neither estrogen deprivation nor estrogen replacement altered Aβ accumulation in the hippocampus or neocortex. Similarly, immunoreactivity for full-length human APP and secreted APPα was unchanged. Estrogen status of the animals was confirmed using a variety of techniques, including uterine and pituitary weight, vaginal cytology, and plasma estradiol concentrations. There was no correlation between plasma estradiol levels and accumulation of either Aβ 1–40 or Aβ 1–42 in the brain. Our observations indicate that long-term estrogen therapy does not alter amyloid pathology in PDAPP mice, an animal model of Alzheimer’s disease, and question the role of estrogen in Aβ deposition in brain.


2004 ◽  
Vol 1 (4) ◽  
pp. 327-338 ◽  
Author(s):  
MICHAEL FOY ◽  
MICHEL BAUDRY ◽  
RICHARD THOMPSON

During the past several years, there has been increasing interest in the effects of estrogen on neural function. This enthusiasm is driven, in part, by the results of early clinical studies suggesting that estrogen therapy given after menopause may prevent, or at least delay, the onset of Alzheimer's disease in older women. However, later clinical trials of women with probable Alzheimer's disease had contrary results. Much of the current research related to estrogen and brain function is focused in two directions. One involves clinical studies that examine the potential of estrogen in protecting against cognitive decline during normal aging and against Alzheimer's disease (neuroprotection). The other direction, which is the primary focus of this review, involves laboratory studies that examine the mechanisms by which estrogen can modify the structure of nerve cells and alter the way neurons communicate with other cells in the brain (neuroplasticity). In this review, we examine recent evidence from experimental and clinical research on the rapid effects of estrogen on several mechanisms that involve synaptic plasticity in the nervous system, including hippocampal excitability, long-term potentiation and depression related to sex and aging differences, cellular neuroprotection and probable molecular mechanisms of the action of estrogen in brain tissue.


Aging Health ◽  
2006 ◽  
Vol 2 (6) ◽  
pp. 955-966 ◽  
Author(s):  
Julie Dumas ◽  
Christy Edgren ◽  
Paul Newhouse

2020 ◽  
Vol 3 (11) ◽  
pp. 34-36
Author(s):  
Thekkuttuparambil Ananthanarayanan Ajith

2019 ◽  
Vol 42 ◽  
Author(s):  
Colleen M. Kelley ◽  
Larry L. Jacoby

Abstract Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.


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