Tau is required for progressive synaptic and memory deficits in a transgenic mouse model of α-synucleinopathy

AbstractParkinson ’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are clinically and neuropathologically highly related α-synucleinopathies that collectively constitute the second leading cause of neurodegenerative dementias. Genetic and neuropathological studies directly implicate α-synuclein (αS) abnormalities in PDD and DLB pathogenesis. However, it is currently unknown how αS abnormalities contribute to memory loss, particularly since forebrain neuronal loss in PDD and DLB is less severe than in Alzheimer’s disease. Previously, we found that familial Parkinson’s disease-linked human mutant A53T αS causes aberrant localization of the microtubule-associated protein tau to postsynaptic spines in neurons, leading to postsynaptic deficits. Thus, we directly tested if the synaptic and memory deficits in a mouse model of α-synucleinopathy (TgA53T) are mediated by tau. TgA53T mice ex hibit progressive memory deficits associated with postsynaptic deficits in the absence of obvious neuropathological and neurodegenerative changes in the hippocampus. Significantly, removal of endogenous mouse tau expression in TgA53T mice (TgA53T/mTau−/−), achieved by mating TgA53T mice to mouse tau-knockout mice, completely ameliorates cognitive dysfunction and concurrent synaptic deficits without affecting αS expression or accumulation of selected toxic αS oligomers. Among the known tau-dependent effects, me...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Fall prevention requires a multifaceted approach that should include individual risk assessment and intervention strategies. Exercise interventions may mitigate most risk factors for falls (eg, balance impairment, gait impairment, and muscle weakness). Numerous systematic reviews or meta-analyses have assessed the effectiveness of exercise interventions among people with various types of neurological disorders; however, the evidence obtained has not been synthesized into an overview. Therefore, the present systematic review assessed systematic reviews of exercise intervention for fall prevention among people with neurologi...
Source: American Journal of Physical Medicine and Rehabilitation - Category: Rehabilitation Tags: Literature Review Source Type: research
Publication date: October 2019Source: European Psychiatry, Volume 62Author(s): Ahmed Naguy, Mohamed S Hashem, Sulaiman AlKhadhar
Source: European Psychiatry - Category: Psychiatry Source Type: research
Publication date: Available online 18 September 2019Source: Neuroscience LettersAuthor(s): Leonardo PignataroAbstractAlthough alcohol abuse and dependence have profound negative health consequences, emerging evidence suggests that exposure to low/moderate concentrations of ethanol protects multiple organs and systems. In the CNS, moderate drinking decreases the risk of dementia and Alzheimer’s disease. This neuroprotection correlates with an increased expression of the heat shock proteins (HSPs). Multiple epidemiological studies revealed an inverse association between ethanol intoxication and traumatic brain injury m...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
Publication date: Available online 18 September 2019Source: NeuronAuthor(s): Peter Dongmin Sohn, Cindy Tzu-Ling Huang, Rui Yan, Li Fan, Tara E. Tracy, Carolina M. Camargo, Kelly M. Montgomery, Taylor Arhar, Sue-Ann Mok, Rebecca Freilich, Justin Baik, Manni He, Shiaoching Gong, Erik D. Roberson, Celeste M. Karch, Jason E. Gestwicki, Ke Xu, Kenneth S. Kosik, Li GanSummaryDysregulation of neuronal excitability underlies the pathogenesis of tauopathies, including frontotemporal dementia (FTD) with tau inclusions. A majority of FTD-causing tau mutations are located in the microtubule-binding domain, but how these mutations alte...
Source: Neuron - Category: Neuroscience Source Type: research
Authors: Childress AC, Chow H Abstract Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder known to respond to amphetamine (AMPH). Multiple AMPH formulations have been developed during the past two decades and have focused mainly on extending the duration of effect. AMPH extended-release oral suspension, Dyanavel XR, (AMPH EROS) was developed to address the unmet needs of patients who have difficulty swallowing intact extended-release (ER) tablets and capsules. Areas covered: The pharmacokinetic profile of the AMPH EROS in children and adults is discussed along with th...
Source: Expert Review of Clinical Pharmacology - Category: Drugs & Pharmacology Tags: Expert Rev Clin Pharmacol Source Type: research
Abstract Pharmaceuticals which originally were designed to treat people with neurological and psychiatric conditions, e.g. Alzheimer's disease or attention deficit hyperactivity disorder (ADHD), are nowadays often misused by students as a 'brain doping' substances. These substances are known as nootropic drugs, smart drugs or cognitive enhancers, as they increase memory, attention and concentration of healthy individuals. Since they are easily available illicitly, their consumption is observed to be growing. Currently, these pharmaceuticals started gaining researchers' attention, especially since they have been re...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
AbstractSporadic late-onset Alzheimer ’s disease (LOAD), the most common form of dementia in the elderly, causes progressive and severe loss of cognitive abilities. With greater numbers of people living to advanced ages, LOAD will increasingly burden both the healthcare system and society. There are currently no available disease-modi fying therapies, and the failure of several recent pathology-based strategies has highlighted the urgent need for effective therapeutic targets. With aging as the greatest risk factor for LOAD, targeting mechanisms by which aging contributes to disease could prove an effective strategy ...
Source: Neurotherapeutics - Category: Neurology Source Type: research
Conclusion Correct diagnosis and specific dietary treatment is crucial to ensure a good prognosis in patients with hypercitrullinaemia. This should be considered as a differential diagnosis in patients with persistent non-hepatic hyperammonaemia. There might be as yet unrecognised gene defects responsible for hypercitrullinaemia.
Source: Journal of Neurology, Neurosurgery and Psychiatry - Category: Neurosurgery Authors: Tags: Genetics, Dementia, Epilepsy and seizures, Drugs: psychiatry, Radiology, Radiology (diagnostics) ABN Annual Meeting, 17-19 May 2016, The Brighton Centre, Brighton Source Type: research
Conclusion In closing, our patient’s episode of TGA combined with her emotional and perceptual response lends credence to the proposal of a “fear/paranoia” circuit in the genesis of paranoid delusions—a circuit incorporating amygdala, frontal, and parietal cortices. Here, neutral or irrelevant stimuli, thoughts, and percepts come to engender fear and anxiety, while dysfunction in frontoparietal circuitry engenders inappropriate social predictions and maladaptive inferences about the intentions of others.[54] Hippocampus relays information about contextual information based on past experiences and th...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Anxiety Disorders Behavioral and Cognitive Neurology Case Report Cognition Current Issue Dementia Medical Issues Neurologic Systems and Symptoms Psychiatry Schizophrenia delusions hippocampus neurobiology Transient global amnesia Source Type: research
Conclusion Healthcare providers in general, and specifically those in the mental health and substance abuse fields, should keep in mind that nootropic use is an under recognized and evolving problem. Nootropic use should be considered in cases where there are sudden or unexplained exacerbations of psychiatric symptoms in patients who have been stable and medication adherent. It is also important to remember that most nootropics are not detected on standard drug toxicology screening tests. We have very little clinical information on how nootropics may interact with psychotropics (or other medications) and potentially cause ...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Case Series and Literature Review Current Issue Mental Disorders Psychiatry Psychopharmacology Substance Use Disorders Ampakines Armodafinil brain enhancer Cerebrolysin Citicoline cognitive enhancer homeopathic medicine natural r Source Type: research
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