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Several hypotheses have been proposed attempting to explain the pathogenesis of Alzheimer disease including, among others, theories involving amyloid deposition, tau phosphorylation, oxidative stress, metal ion dysregulation and inflammation. While there is strong evidence suggesting that each one of these proposed mechanisms contributes to disease(More)
Until recently, the study of hormonal influences in Alzheimer disease was limited to the role of sex steroids. Despite numerous epidemiological studies supporting a protective role for estrogen in Alzheimer disease, recent studies show that estrogen administration in elderly women increases the risk of disease. Reconciling these contradictory reports, we(More)
Questions surrounding estrogen therapy for post-menopausal cognitive decline and dementia led us to examine the role of luteinizing hormone that becomes elevated after menopause. We examined hippocampal-associated cognitive performance, as measured with the Y-maze task, in two strains of transgenic mice, one (Tg-LHbeta) which over-expresses luteinizing(More)
In this review, we discuss the role of cell cycle dysfunction in the pathogenesis of Alzheimer disease and propose that such mitotic catastrophe, as one of the earliest events in neuronal degeneration, may, in fact, be sufficient to initiate the neurodegenerative cascade. The question as to what molecule initiates cell cycle dysfunction is now beginning to(More)
Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further(More)
The search for a definitive gender bias in Alzheimer's disease has resulted in a multitude of epidemiological findings that point to a higher prevalence and incidence of Alzheimer's disease in women. Due to this reported predisposition of women to Alzheimer's disease, the sex steroid estrogen has become the primary focus of research in this field, however,(More)
Endothelins and endothelin receptors are widespread in the brain. There is increasing evidence that endothelins play a role in brain mechanisms associated with behaviour and neuroendocrine regulation as well as cardiovascular control. We review the evidence for an interaction of endothelin with brain dopaminergic mechanisms. Our work has shown that(More)
Differences in the prevalence and age of onset of Alzheimer disease (AD) in men and women, and observations that hormone replacement therapy (HRT) may prevent the development of AD, caused many to hypothesize that estrogen deficiency contributes to AD. However, recent trials using estrogen failed to show any benefit in preventing or alleviating the disease.(More)
In recent years, Alzheimer disease (AD) has received great attention as an incurable and fatal disease that threatens the lives of aging individuals. Debates regarding areas of research and treatment designs have made headlines as scientists in the field question ongoing work. Despite these academic quarrels, significant insights concerning the cellular and(More)
Based on epidemiological and observational studies, estrogen and hormone-replacement therapy were until recently viewed as major factors in the prevention of Alzheimer's disease (AD). However, a recent randomized clinical trial revealed that hormone replacement therapy using estrogen plus progestin may actually exacerbate the incidence of dementia when(More)