Yuko Hara

Risk reduction and precision prevention across the Alzheimer’s disease continuum: a systematic review of clinical trials combining multidomain lifestyle interventions and pharmacological or nutraceutical approaches

Erika Bereczki, Francesca Mangialasche, Mariagnese Barbera, P Moreno Padilla et autres

To effectively combat dementia onset and progression, lifestyle-based interventions targeting multiple risk factors and disease mechanisms through a multidomain approach - tailored and implemented early in the disease process - have emerged as promising. Electronic databases and relevant websites (clinicaltrials.gov, euclinicaltrials.eu, PubMed …

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The State of Alzheimer's Research and the Path Forward

Howard Fillit, Bruno Vellas, Yuko Hara

International audience

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Value-Generating Exploratory Trials in Neurodegenerative Dementias

Lauren G. Friedman, Nicholas McKeehan, Yuko Hara, Jeffrey L. Cummings et autres

Drug development for Alzheimer disease and other neurodegenerative dementias, including frontotemporal dementia, has experienced a long history of phase 2 and phase 3 clinical trials that failed to show efficacy of investigational drugs. Despite differences in clinical and behavioral characteristics, these disorders …

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Estrogenic Regulation of Synaptic Health and Cognition in Aging Rhesus Monkeys

Johanna L. Crimins, Yuko Hara, John H. Morrison

Abstract A compelling case can be made for estrogen’s role in maintaining synaptic health in the context of cognitive aging. This chapter first reviews clinical literature pertinent to estrogenic actions on cognition in menopausal women. Next, the authors provide a comprehensive summary …

Translating the biology of aging into novel therapeutics for Alzheimer disease

Yuko Hara, Nicholas McKeehan, Howard Fillit

Aging is the leading risk factor for most chronic illnesses of old age, including Alzheimer disease (AD), a progressive neurodegenerative disease with currently no therapies that prevent, slow, or halt disease progression. Like other chronic diseases of old age, the progressive pathology …

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Estrogen Alters the Synaptic Distribution of Phospho-GluN2B in the Dorsolateral Prefrontal Cortex While Promoting Working Memory in Aged Rhesus Monkeys

Yuko Hara, Johanna L. Crimins, Rishi Puri, Athena C. J. Wang et autres

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Synaptic distributions of pS214‐tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline

Johanna L. Crimins, Rishi Puri, Katina C. Calakos, Frank Yuk et autres

Female rhesus monkeys and women are subject to age- and menopause-related deficits in working memory, an executive function mediated by the dorsolateral prefrontal cortex (dlPFC). Long-term cyclic administration of 17β-estradiol improves working memory, and restores highly plastic axospinous synapses within layer III …

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Astrocytic tight junctions control inflammatory CNS lesion pathogenesis

Sam Horng, Anthony Therattil, Sarah Moyon, Alexandra Gordon et autres

Lesions and neurologic disability in inflammatory CNS diseases such as multiple sclerosis (MS) result from the translocation of leukocytes and humoral factors from the vasculature, first across the endothelial blood-brain barrier (BBB) and then across the astrocytic glia limitans (GL). Factors secreted …

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EVALUATION OF THE NEUROPROTECTIVE POTENTIAL OF N-ACETYLCYSTEINE FOR PREVENTION AND TREATMENT OF COGNITIVE AGING AND DEMENTIA

Yuko Hara, Howard Fillit, Penny A. Dacks, Nicholas McKeehan

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Involvement of the Septo-Hippocampal Cholinergic Pathway in Association with Septal Acetylcholinesterase Upregulation in a Mouse Model of Tauopathy

Yuko Hara, Yumiko Motoi, Keigo Hikishima, Hiroshi Mizuma et autres

BACKGROUND: Cholinergic cell loss in the basal forebrain, the major source of hippocampal cholinergic projections, has been implicated in Alzheimer's disease. OBJECTIVE: To examine whether the septohippocampal pathway is involved in tauopathy model mice and to elucidate the tau-associated mechanism underlying cholinergic …

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The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination

Benjamin M. Laitman, Linnéa Asp, John N. Mariani, Jingya Zhang et autres

Growth factors of the gp130 family promote oligodendrocyte differentiation, and viability, and myelination, but their mechanisms of action are incompletely understood. Here, we show that these effects are coordinated, in part, by the transcriptional activator Krüppel-like factor-6 (Klf6). Klf6 is rapidly induced …

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The Transcriptional Activator Krüppel-Like Factor-6 Is Required for CNS Myelination (S10.007)

Benjamin M. Laitman, Linnéa Asp, John N. Mariani, Jingya Zhang et autres

Objective: To determine the mechanism of action of Krüppel-like factor-6 (Klf6), a transcription factor found to be important for myelination. Background: Oligodendrocyte progenitors (OLP) are the main reservoir of myelinating and remyelinating cells in the CNS. Their differentiation into myelinating oligodendrocytes (OL) …

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