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alzheimers prevention

Paula Castro, Shahid Zaman, Anthony Holland
People with Down's syndrome (DS) are at high risk for developing Alzheimer's disease (AD) at a relatively young age. This increased risk is not observed in people with intellectual disabilities for reasons other than DS and for this reason it is unlikely to be due to non-specific effects of having a neurodevelopmental disorder but, instead, a direct consequence of the genetics of DS (trisomy 21). Given the location of the amyloid precursor protein (APP) gene on chromosome 21, the amyloid cascade hypothesis is the dominant theory accounting for this risk, with other genetic and environmental factors modifying the age of onset and the course of the disease...
October 24, 2016: Journal of Neurology
Elijah Mak, Silvy Gabel, Habib Mirette, Li Su, Guy B Williams, Adam Waldman, Katie Wells, Karen Ritchie, Craig Ritchie, John O'Brien
The last decade has witnessed a proliferation of neuroimaging studies characterising brain changes associated with Alzheimer's disease (AD), where both widespread atrophy and 'signature' brain regions have been implicated. In parallel, a prolonged latency period has been established in AD, with abnormal cerebral changes beginning many years before symptom onset. This raises the possibility of early therapeutic intervention, even before symptoms, when treatments could have the greatest effect on disease-course modification...
October 21, 2016: Ageing Research Reviews
Hong-Yan Cai, Zhao-Jun Wang, Christian Hölscher, Li Yuan, Jun Zhang, Peng Sun, Jing Li, Wei Yang, Mei-Na Wu, Jin-Shun Qi
Type 2 diabetes mellitus(T2DM) is a risk factor of Alzheimer's disease (AD), which is most likely linked to impairments of insulin signaling in the brain. Hence, drugs enhancing insulin signaling may have therapeutic potential for AD. Lixisenatide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analogue, facilitates insulin signaling and has neuroprotective properties. We previously reported the protective effects of lixisenatide on memory formation and synaptic plasticity. Here, we describe additional key neuroprotective properties of lixisenatide and its possible molecular and cellular mechanisms against AD-related impairments in rats...
October 21, 2016: Behavioural Brain Research
J Phillip Turner, Shelby E Chastain, Dongwon Park, Melissa A Moss, Shannon L Servoss
Alzheimer's disease (AD) is characterized by the buildup of insoluble aggregated amyloid-β protein (Aβ) into plaques that accumulate between the neural cells in the brain. AD is the sixth leading cause of death in the United States and is the only cause of death among the top ten that cannot currently be treated or cured (Alzheimer's Association, 2011; Selkoe, 1996). Researchers have focused on developing small molecules and peptides to prevent Aβ aggregation; however, while some compounds appear promising in vitro, the research has not resulted in a viable therapeutic treatment...
October 10, 2016: Bioorganic & Medicinal Chemistry
Paulina R Davis, Ginevra Giannini, Karin Rudolph, Nathaniel Calloway, Christopher M Royer, Tina L Beckett, M Paul Murphy, Frederick Bresch, Dieter Pagani, Thomas Platt, Xiaohong Wang, Amy Skinner Donovan, Tiffany L Sudduth, Wenjie Lou, Erin Abner, Richard Kryscio, Donna M Wilcock, Edward G Barrett, Elizabeth Head
Beta-amyloid (Aβ) immunotherapy is a promising intervention to slow Alzheimer's disease. Aging dogs naturally accumulate Aβ and show cognitive decline. An active vaccine against fibrillar Aβ 1-42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aβ. Behavioral enrichment (ENR) led to cognitive benefits but no reduction in Aβ. We hypothesized cognitive outcomes could be improved by combining VAC with ENR in aged dogs. Aged dogs (11-12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); and (4) ENR/VAC (E/V) and treated for 20 months...
September 26, 2016: Neurobiology of Aging
Chien-Li Chen, Wen-Hao Tsai, Chun-Jen Chen, Tzu-Ming Pan
Centella asiatica ( léi gōng gēn) is a traditional medicinal herb with high antioxidant activity, which decreases amyloid-β (Aβ) deposition in the brain. At the same time, aggregated Aβ-induced oxidative stress is the trigger in the pathogenesis of Alzheimer's disease (AD). Here, we investigated the ability of C. asiatica ethanol extract (CAE) to protect PC12 and IMR32 cells from Aβ1-40-induced production of reactive oxygen species (ROS) and concomitant neurotoxicity. Aggregated Aβ1-40 treatment resulted in reduced cell viability, which can be reversed by cotreatment with 25, 50, and 100 μg/mL CAE...
October 2016: Journal of Traditional and Complementary Medicine
Bonnie Au, Sydney Dale-McGrath, Mary C Tierney
OBJECTIVE: More women have Alzheimer's disease (AD) than men. Understanding sex differences in mild cognitive impairment (MCI) may further knowledge of AD etiology and prevention. We conducted a meta-analysis to examine sex differences in the prevalence and incidence of MCI, which included amnestic and non-amnestic subtypes. METHOD: Systematic searches were performed in July 2015 using MEDLINE/PubMed, Scopus, and PsycINFO for population-or community-based studies with MCI data for men and women...
October 19, 2016: Ageing Research Reviews
Timothy M Brenza, Shivani Ghaisas, Julia E Vela Ramirez, Dilshan Harischandra, Vellareddy Anantharam, Balaraman Kalyanaraman, Anumantha G Kanthasamy, Balaji Narasimhan
A progressive loss of neuronal structure and function is a signature of many neurodegenerative conditions including chronic traumatic encephalopathy, Parkinson's, Huntington's and Alzheimer's diseases. Mitochondrial dysfunction and oxidative and nitrative stress have been implicated as key pathological mechanisms underlying the neurodegenerative processes. However, current therapeutic approaches targeting oxidative damage are ineffective in preventing the progression of neurodegeneration. Mitochondria-targeted antioxidants were recently shown to alleviate oxidative damage...
October 19, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Da-Shi Qi, Jin-Hao Tao, Lian-Qin Zhang, Mei Wang, Rui Qu, Lian-Qin Zhang, Pei Liu, Jian-Cheng Miu, Jing-Yi Ma, Xin-Yu Mei
Cilostazol(CTL) is a phosphodiesterase inhibitor, which has been widely used as anti-platelet agent. It also has preventive effects on various central nervous system (CNS) diseases, including ischemic stroke, Parkinson's disease and Alzheimer disease. However, the molecular mechanism underlying the protective effects of CTL is still unclear, and whether CTL can prevent I/R induced cognitive deficit has not been reported. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats...
October 18, 2016: Brain Research
Maria Anderson, Feng Xu, Ming-Hsuan Ou-Yang, Judianne Davis, William E Van Nostrand, John K Robinson
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the leading cause of dementia in the elderly. Amyloid-β protein (Aβ) depositions in both the brain parenchyma and the cerebral vasculature are recognized as important pathological components that contribute to the cognitive impairments found in individuals with AD. Because pharmacological options have been minimally effective in treating cognitive impairment to date, interest in the development of preventative lifestyle intervention strategies has increased in the field...
October 19, 2016: Journal of Alzheimer's Disease: JAD
Natarajan Suganthy, Dicson Sheeja Malar, Kasi Pandima Devi
OBJECTIVE: Amyloid hypothesis states that endogenous β-amyloid peptides (Aβ), especially its aggregated oligomers and fibrils are the key pathogenic factors leading to Alzheimer's disease (AD). Therefore, inhibition of Aβ fibrillation rather than blocking its production is considered promising therapeutic intervention. Hence, the present study was carried out to assess the effect of methanolic leaf extract of R. mucronata (MERM) and its bioactive compound catechin on in vitro fibrillation of Aβ (25-35)...
October 21, 2016: Neurological Research
Hossein Derakhshankhah, Mohammad Javad Hajipour, Ebrahim Barzegari, Alireza Lotfabadi, Maryam Ferdousi, Ali Akbar Saboury, Eng-Poh Ng, Mohammad Raoufi, Hussein Awala, Svetlana Mintova, Rassoul Dinarvand, Morteza Mahmoudi
EMT-type zeolite nanoparticles (EMT NPs) with diameter smaller than 12 nm and uniform pore size of 7.3 Å have shown high selective affinity toward plasma protein (fibrinogen). Besides, the EMT NPs have demonstrated no adverse effect on blood coagulation hemostasis. Therefore, it was envisioned that the EMT NPs could inhibit possible β-Amyloid (Aβ)-fibrinogen interactions that result in the formation of structurally abnormal clots, which are resistant to lysis, in cerebral vessels of patients with Alzheimer disease (AD)...
October 21, 2016: ACS Applied Materials & Interfaces
Cinzia Guzzi, Laura Colombo, Ada De Luigi, Mario Salmona, Francesco Nicotra, Cristina Airoldi
Combining NMR spectroscopy, transmission electron microscopy, biochemical and in vitro toxicity assays, we characterized the effect of flavonoid glycosylation, a chemical modification very frequent in Nature, on their ability to recognise and bind Aβ1-42 oligomers, preventing their aggregation and their neurotoxicity. Our data allow the elucidation of their structure activity relationships, showing that glycosylation has a modest impact on flavonoid affinity for Aβ oligomers but, at the same time, increases both solubility and chemical stability, thus promoting their beneficial properties against Alzheimer's diseases (AD)...
October 21, 2016: Chemistry, An Asian Journal
IbDanelo Cortez, Dmitry V Bulavin, Ping Wu, Erica L McGrath, Kathryn A Cunningham, Maki Wakamiya, John Papaconstantinou, Kelly T Dineley
A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α(AF/+)) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α(AF/+)) and kinase activity. As a result, aged DN-p38α(AF/+) mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates...
October 17, 2016: Behavioural Brain Research
Hyeon-Joong Kim, Dae-Joong Kim, Eun-Ju Shin, Byung-Hwan Lee, Sun-Hye Choi, Sung-Hee Hwang, Hyewhon Rhim, Ik-Hyun Cho, Hyoung-Chun Kim, Seung-Yeol Nah
We previously showed that gintonin, an exogenous lysophosphatidic acid (LPA) receptor ligand, attenuated β-amyloid plaque formation in the cortex and hippocampus, and restored β-amyloid-induced memory dysfunction. Both endogenous LPA and LPA receptors play a key role in embryonic brain development. However, little is known about whether gintonin can induce hippocampal cell proliferation in adult wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease (AD). In the present study, we examined the effects of gintonin on the proliferation of hippocampal neural progenitor cells (NPCs) in vitro and its effects on the hippocampal cell proliferation in wild-type mice and a transgenic AD mouse model...
October 17, 2016: Neurochemistry International
Sumihiro Maeda, Lennart Mucke
Lasagna-Reeves et al. (2016) demonstrate that preventing the kinase Nuak1 from phosphorylating the microtubule-associated protein tau reduces the level of potentially pathogenic tau species in brain, a novel therapeutic strategy that could help counteract Alzheimer's disease and several other neurological disorders.
October 19, 2016: Neuron
Marissa B Guzzo, Hoa T Nguyen, Thanh H Pham, Monika Wyszczelska-Rokiel, Hieronim Jakubowski, Kerstin A Wolff, Sam Ogwang, Joseph L Timpona, Soumya Gogula, Michael R Jacobs, Markus Ruetz, Bernhard Kräutler, Donald W Jacobsen, Guo-Fang Zhang, Liem Nguyen
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis...
October 2016: PLoS Pathogens
Rosario Gajardo-Gómez, Valeria C Labra, Carola J Maturana, Kenji F Shoji, Cristian A Santibañez, Juan C Sáez, Christian Giaume, Juan A Orellana
The mechanisms involved in Alzheimer's disease are not completely understood and how astrocytes and their gliotransmission contribute to this neurodegenerative disease remains to be fully elucidated. Previous studies have shown that amyloid-β peptide (Aβ) induces neuronal death by a mechanism that involves the excitotoxic release of ATP and glutamate associated to astroglial hemichannel opening. We have demonstrated that synthetic and endogenous cannabinoids (CBs) reduce the opening of astrocyte Cx43 hemichannels evoked by activated microglia or inflammatory mediators...
October 19, 2016: Glia
M Florencia Iulita, Hélène Girouard
Hypertension and dementia are two of the most prevalent and damaging diseases associated with aging. Chronic hypertension, particularly during mid-life, is a strong risk factor for late-life cognitive decline and impairment. Hypertension is also the number one risk factor for stroke and a major contributor to the pathogenesis of vascular dementia and Alzheimer's disease. Despite the vast epidemiologic and mechanistic evidence linking hypertension to cognitive impairment, and the positive effects of blood pressure lowering on reducing the risk of post-stroke dementia, uncertainty remains about the benefit of antihypertensive medication on other forms of dementia...
October 19, 2016: Advances in Experimental Medicine and Biology
Zhiyou Cai, Chuanling Wang, Wenming Yang
Berberine, an important protoberberine isoquinoline alkaloid, has several pharmacological activities, including antimicrobial, glucose- and cholesterol-lowering, antitumoral, and immunomodulatory properties. Substantial studies suggest that berberine may be beneficial to Alzheimer's disease (AD) by limiting the pathogenesis of extracellular amyloid plaques and intracellular neurofibrillary tangles. Increasing evidence has indicated that berberine exerts a protective role in atherosclerosis related to lipid- and glucose-lowering properties, implicating that berberine has the potential to inhibit these risk factors for AD...
2016: Neuropsychiatric Disease and Treatment
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