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Start Over Author "Smith, Mark" Journal journal of alzheimer's disease
204 results on '"Smith, Mark"'

2. Putative Gonadotropin-Releasing Hormone Agonist Therapy and Dementia: An Application of Medicare Hospitalization Claims Data.

Author

Atwood, Craig S., Rimm, Alfred A., Smith, Mark A., Bowen, Richard L., Nguyen, Richard Q., and Perry, George

Subjects
GONADOTROPIN releasing hormone, CHEMICAL agonists, DEMENTIA, MEDICARE, HOSPITAL care, INSURANCE claims, ALZHEIMER'S disease, THERAPEUTICS
Abstract

Background: Estrogen and hormone replacement therapies to reduce Alzheimer's disease (AD) have yielded conflicting results. However, this study proposes that the well-characterized increase in serum gonadotropins following menopause or andropause are accountable for the increased risk of developing AD among the elderly population.Objective: To determine the role of gonadotropins in the development of AD and investigate gonadotropin-releasing hormone (GnRH) agonist therapy as a potential preventative and/or disease-modifying approach to AD management.Methods: Male Medicare beneficiaries aged 67 to 75 and hospitalized with prostate cancer (n = 115,789) were compared to three control groups: men of the same demographics undergoing a cholecystectomy (n = 97,267), herniorrhaphy (n = 68,778), or transurethral prostatectomy (n = 267,691). A proportion of the patients hospitalized with prostate cancer were assumed to have low concentrations of serum gonadotropins and sex steroids as a result of GnRH agonist therapy, while those in the control groups were assumed to have elevated gonadotropin but lowered sex steroid levels that are associated with andropause in this age group.Results: The rates of development of select diagnoses of dementia, including AD, over a twelve-year follow-up period following surgery. When compared to control patients, men hospitalized with prostate cancer have a protection against dementia after twelve years of follow-up, with relative risks ranging from 0.48 to 0.83.Conclusion: Patients with prostate cancer are treated with the GnRH analogue leuprolide acetate, our data suggest that leuprolide acetate may be therapeutic for AD via its downregulation of serum gonadotropins. [ABSTRACT FROM AUTHOR]

Published
2018
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16. Early Amyloid Accumulation in the Hippocampus of SAMP8 Mice

Author

del Valle, Jaume, primary, Duran-Vilaregut, Joaquim, additional, Manich, Gemma, additional, Casadesús, Gemma, additional, Smith, Mark A., additional, Camins, Antoni, additional, Pallàs, Mercè, additional, Pelegrí, Carme, additional, and Vilaplana, Jordi, additional

Published
2010
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17. Increased Iron and Free Radical Generation in Preclinical Alzheimer Disease and Mild Cognitive Impairment

Author

Smith, Mark A., primary, Zhu, Xiongwei, additional, Tabaton, Massimo, additional, Liu, Gang, additional, McKeel, Daniel W., additional, Cohen, Mark L., additional, Wang, Xinglong, additional, Siedlak, Sandra L., additional, Dwyer, Barney E., additional, Hayashi, Takaaki, additional, Nakamura, Masao, additional, Nunomura, Akihiko, additional, and Perry, George, additional

Published
2010
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18. Insulin is a Two-Edged Knife on the Brain

Author

Cardoso, Susana, primary, Correia, Sónia, additional, Santos, Renato X., additional, Carvalho, Cristina, additional, Santos, Maria S., additional, Oliveira, Catarina R., additional, Perry, George, additional, Smith, Mark A., additional, Zhu, Xiongwei, additional, and Moreira, Paula I., additional

Published
2009
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20. Leptin: A Novel Therapeutic Strategy for Alzheimer's Disease

Author

Tezapsidis, Nikolaos, primary, Johnston, Jane M., additional, Smith, Mark A., additional, Ashford, J. Wesson, additional, Casadesus, Gemma, additional, Robakis, Nikolaos K., additional, Wolozin, Benjamin, additional, Perry, George, additional, Zhu, Xiongwei, additional, Greco, Steven J., additional, and Sarkar, Sraboni, additional

Published
2009
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25. Three-Dimensional Tomographic Imaging and Characterization of Iron Compounds within Alzheimer's Plaque Core Material

Author

Collingwood, Joanna F., primary, Chong, Ryan K. K., additional, Kasama, Takeshi, additional, Cervera-Gontard, Lionel, additional, Dunin-Borkowski, Rafal E., additional, Perry, George, additional, Pósfai, Mihály, additional, Siedlak, Sandra L., additional, Simpson, Edward T., additional, Smith, Mark A., additional, and Dobson, Jon, additional

Published
2008
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46. Abnormal Mitochondrial Dynamics in the Pathogenesis of Alzheimer's Disease.

Author

Zhu, Xiongwei, Perry, George, Smith, Mark A., and Wang, Xinglong

Subjects
ALZHEIMER'S disease, NEURONS, MITOCHONDRIAL pathology, BRAIN, BASAL ganglia diseases
Abstract

Mitochondrial dysfunction is one of the most early and prominent features in vulnerable neurons in the brain of Alzheimer's disease (AD) patients. Recent studies suggest that mitochondria are highly dynamic organelles characterized by a delicate balance of fission and fusion, a concept that has revolutionized our basic understanding of the regulation of mitochondrial structure and function which has far-reaching significance in studies of health and disease. Tremendous progress has been made in studying changes in mitochondrial dynamics in AD brain and models and the potential underlying mechanisms. This review highlights the recent work demonstrating abnormal mitochondrial dynamics and distribution in AD models and discusses how these abnormalities may contribute to various aspects of mitochondrial dysfunction and the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Published
2013

47. Tau Transgenic Mice as Models for Cerebrospinal Fluid Tau Biomarkers.

Author

Britton, Gabriel B., Smith, Mark A., Perry, George, Sambamurti, Kumar, Jagannatha Rao, K.S., Barten, Donna M., Cadelina, Gregory W., Hoque, Nina, DeCarr, Lynn B., Guss, Valerie L., Yang, Ling, Sankaranarayanan, Sethu, Wes, Paul D., Flynn, Marianne E., Meredith, Jere E., Ahlijanian, Michael K., and Albright, Charles F.

Subjects
*CEREBROSPINAL fluid, *BIOMARKERS, *ALZHEIMER'S disease, *TRANSGENIC mice, *NEURONS
Abstract

Levels of tau in cerebrospinal fluid (CSF) are elevated in Alzheimer's disease (AD) patients. It is believed this elevation is related to the tau pathology and neurodegeneration observed in AD, but not all tauopathies have increased CSF tau. There has been little pre-clinical work to investigate mechanisms of increased CSF tau due to the difficulty in collecting CSF samples from mice, the most commonly used pre-clinical models. We developed methods to collect CSF from mice without contamination from tau in brain tissue, which is approximately 50,000 fold more abundant in brain than CSF. Using these methods, we measured CSF tau from 3xTg, Tg4510, and Tau Alone transgenic mice. All three lines of mice showed age-dependent increases in CSF tau. They varied in phenotype from undetectable to severe tau pathology and neurodegeneration, suggesting that degenerating neurons are unlikely to be the only source of pathologic CSF tau. Overall, CSF tau levels mirrored expression levels and changes of tau in the brain, but they did not always correlate exactly. CSF tau was often more sensitive to changes in brain transgene expression and pathology. In addition, we also developed ELISA assays specific to different regions of the tau protein. We used these assays to provide evidence that CSF tau exists as fragments, with little intact C-terminus and partial loss of the N-terminus. Taken together, these assays and mouse models may be used to facilitate a deeper understanding of CSF tau in neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Published
2011

48. Activation of the α-Secretase Processing of AβPP as a Therapeutic Approach in Alzheimer's Disease.

Author

Britton, Gabriel B., Smith, Mark A., Perry, George, Sambamurti, Kumar, Jagannatha Rao, K.S., Vincent, Bruno, and Govitrapong, Piyarat

Subjects
*ALZHEIMER'S disease, *SECRETASES, *AMYLOID, *DISEASES in older people, *NEURODEGENERATION, *AMINO acid sequence
Abstract

Alzheimer's disease (AD) is by far the main cause of dementia in the aged population. Because the amyloid-β peptide (Aβ) is the main component of senile plaques that develop in the brain of affected patients, numerous studies aimed at preventing its production or aggregation were conducted during the past 25 years. The inhibition of Aβ production via pharmacological inhibition of β- and γ-secretases is, with vaccination, one of the two main current challenges aimed at curing AD. However, the fact that there exist numerous substrates of these two activities renders this approach problematic since treatments with β- or γ-secretase inhibitors can cause deleterious effects. An alternative to the inhibition of the amyloidogenic enzymes would be to activate the α-secretase processing of AβPP. This cleavage is performed by two members of the disintegrin family of metalloproteases (ADAM10 and ADAM17). It is noteworthy that this cleavage can be seen as doubly beneficial regarding AD since it both occurs in the middle of the Aβ sequence and triggers the release of the neuroprotective sAβPPα product. However, similarly to β- and γ-secretases, ADAM10 and ADAM17 are responsible for the cleavage of a large number of proteins, the processing of some of them being tightly associated with important physiological functions but also with severe pathologies. This review focuses on our current knowledge of the various natural or synthetic compounds able to trigger α-secretase activities and on the possible ways to circumvent the deleterious side effects that would result from their broad activation. [ABSTRACT FROM AUTHOR]

Published
2011

49. Humanin Signal for Alzheimer's Disease.

Author

Britton, Gabriel B., Smith, Mark A., Perry, George, Sambamurti, Kumar, Jagannatha Rao, K.S., and Matsuoka, Masaaki

Subjects
*ALZHEIMER'S disease, *NEURONS, *DISEASE progression, *TRANSGENIC mice, *BIOACTIVE compounds, *PEPTIDES
Abstract

Despite a bulk of evidence supporting the idea that increased neurotoxic insults lead to Alzheimer's disease (AD), the possibility still remains that insufficiency of an endogenous defense system contributes to the disease progression. Humanin is a bioactive peptide that is likely to inhibit both neuronal death and dysfunction only related to AD by binding to a Humanin receptor on the cell-surface and by activating a STAT3-mediated signal, preventing the onset of dementia. A couple of recent studies presented evidence suggesting that the Humanin signal is decreased in neurons of AD patients. If this is the case, the restoration or activation of the Humanin signal in neurons may change the course of AD. [ABSTRACT FROM AUTHOR]

Published
2011

50. Oxidative Stress Treatment for Clinical Trials in Neurodegenerative Diseases.

Author

Britton, Gabriel B., Smith, Mark A., Perry, George, Sambamurti, Kumar, Jagannatha Rao, K.S., Ienco, Elena Caldarazzo, LoGerfo, Annalisa, Carlesi, Cecilia, Orsucci, Daniele, Ricci, Giulia, Mancuso, Michelangelo, and Siciliano, Gabriele

Subjects
*OXIDATIVE stress, *METABOLIC syndrome, *ANTIOXIDANTS, *CLINICAL trials, *TREATMENT of neurodegeneration
Abstract

Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine. [ABSTRACT FROM AUTHOR]

Published
2011

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