EDITOR’S CHOICE – Tolfenamic Acid: A Modifier of the Tau Protein and its Role in Cognition and Tauopathy

Journal: Current Alzheimer Research

Author(s): Lingyu Lee*, Yingli Liu


Background: Tangles are deposits of hyperphosphorylated tau, which are found in multiple neurodegenerative disorders that are referred to as tauopathies, of which Alzheimer’s disease (AD) is the most common. Tauopathies are clinically characterized by dementia and share common cortical lesions composed of aggregates of the protein tau.

Objective: In this study, we explored the therapeutic potential of tolfenamic acid (TA), in modifying disease processes in a transgenic animal model that carries the human tau gene (hTau).

Methods: Behavioral tests, Western blotting and Immunohistochemical analysis were used to demonstrate the efficacy of TA.

Results: Treatment of TA improved improving spatial learning deficits and memory impairments in young and aged hTau mice. Western blot analysis of the hTau protein revealed reductions in total tau as well as in sitespecific hyperphosphorylation of tau in response to TA administration. Immunohistochemical analysis for phosphorylated tau protein revealed reduced staining in the frontal cortex, hippocampus, and striatum in animals treated with TA.

Conclusion: TA holds the potential as a disease-modifying agent for the treatment of tauopathies including AD.

Read more here: http://www.eurekaselect.com/159193/article



Current Inorganic Chemistry 7, Issue 2

Current Cardiology Reviews 14, Issue 1

Current Proteomics 15, Issue 2

Mini-Reviews in Organic Chemistry 15, Issue 2

Current Alzheimer Research 15, Issue 5

Current Diabetes Reviews 14, Issue 2


EDITOR’S CHOICE – Up-regulation of DMN Connectivity in Mild Cognitive Impairment Via Network-based Cognitive Training – Current Alzheimer Research

Journal: Current Alzheimer Research

Author(s): Matteo De Marco, Francesca Meneghello, Cristina Pilosio, Jessica Rigon, Annalena Venneri*


Background: Previous work designed a network-based protocol of cognitive training. This programme exploits a mechanism of induced task-oriented co-activation of multiple regions that are part of the default mode network (DMN), to induce functional rewiring and increased functional connectivity within this network.

Objective: In this study, the programme was administered to patients with a diagnosis of mild cognitive impairment to test its effects in a clinical sample.

Method: Twenty-three patients with mild cognitive impairment (mean age: 73.74 years, standard deviation 5.13, female/male ratio 13/10) allocated to the experimental condition, underwent one month of computerised training, while fourteen patients (mean age: 73.14 years, standard deviation 6.16, female/ male ratio 7/7) assigned to the control condition underwent a regime of intense social engagement. Patients were in the prodromal stage of Alzheimer’s disease (AD) as confirmed by clinical follow ups for at least two years. The DMN was computed at baseline and retest, together with other, control patterns of connectivity, grey matter maps and neuropsychological profiles.

Results: A condition-by-timepoint interaction indicating increased connectivity triggered by the programme was found in left parietal DMN regions. No decreases as well as no changes in the other networks or morphology were found. Although between-condition cognitive changes did not reach statistical significance, they correlated positively with changes in DMN connectivity in the left parietal region, supporting the hypothesis that parietal changes were beneficial.

Conclusion: This programme of cognitive training up-regulates a pattern of connectivity which is pathologically down-regulated in AD. We argue that, when cognitive interventions are conceptualised as tools to induce co-activation repeatedly, they can lead to clinically relevant improvements in brain functioning, and can be of aid in support of pharmacological and other interventions in the earliest stages of AD.

Read more here: http://www.eurekaselect.com/158224/article




Current Pharmacogenomics and Personalized Medicine 15-2


Current Medicinal Chemistry 25-6


Current Alzheimer Research 15-4


Current Topics in Medicinal Chemistry 17-32


Current Stem Cell Research & Therapy 13-3




Anti-Infective Agents Volume 15, Issue 2

Current Alzheimer Research Volume 15, Issue 3

Recent Advances in Electrical & Electronic Engineering Volume 11, Issue 1

Current Women`s Health Reviews Volume 14, Issue 1

Current Neuropharmacology Volume 16, Issue 2

Letters in Drug Design & Discovery Volume 15, Issue 2

Letters in Drug Design & Discovery Volume 15, Issue 3


EDITOR’S CHOICE – Ongoing Electroencephalographic Activity Associated with Cortical Arousal in Transgenic PDAPP Mice (hAPP V717F) – Current Alzheimer Research

Journal: Current Alzheimer Research

Author(s): Claudio Del Percio, Wilhelmus Drinkenburg, Susanna Lopez, Cristina Limatola, Jesper F. Bastlund,Ditte Z. Christensen, Jan T. Pedersen, Gianluigi Forloni, Angelisa Frasca, Francesco M. Noe, Marina Bentivoglio, Paolo F. Fabene, Giuseppe Bertini, Valeria Colavito, Sophie Dix, Raffaele Ferri, Regis Bordet, Jill C. Richardson, Claudio Babiloni


Background: It has been shown that theta (6-10 Hz) and delta (1-6 Hz) ongoing electroencephalographic (EEG) rhythms revealed variations in the cortical arousal in C57 Wild Type (WT) mice during cage exploration (active condition) compared to awake quiet behavior (passive condition; IMI PharmaCog project, http://www.pharmacog.eu).

Objective: The objective was to test if these EEG rhythms might be abnormal in old PDAPP mice modeling Alzheimer’s disease (AD) with a hAPP Indiana V717F mutation (They show abnormal neural transmission, cognitive deficits, and brain accumulation of Aβ1-42).

Methods: Ongoing EEG rhythms were recorded by a frontoparietal bipolar channel in 15 PDAPP and 23 WT C57 male mice (mean age of 22.8 months ±0.4 and 0.3 standard error, respectively). EEG absolute power (density) was calculated. Frequency and amplitude of individual delta and theta frequency (IDF and ITF) peaks were considered during passive and active states in the wakefulness.

Results: Compared with the WT group, the PDAPP group showed higher frequency of the IDF during the passive condition and lower frequency of the ITF during the active state. Furthermore, the WT but not PDAPP group showed significant changes in the frontoparietal EEG power (IDF, ITF) during active over passive state.

Conclusion: PDAPP mice were characterized by less changes in the brain arousal during an active state as revealed by frontoparietal EEG rhythms. Future studies will have to cross-validate the present results on large animal groups, clarify the neurophysiological underpinning of the effect, and test if the disease modifying drugs against AD amyloidosis normalize those candiate EEG biomarkers in PDAPP mice

Read more here: http://www.eurekaselect.com/153722


HIGHLIGHTED ARTICLE – Decrease in the Generation of Amyloid-β Due to Salvianolic Acid B by Modulating BACE1 Activity – CURRENT ALZHEIMER RESEARCH

CAR-Articles_14-12-Siva Sundara Kumar.jpg

To access the article, please visit: http://www.eurekaselect.com/151645/article

NEW ISSUE :: Current Alzheimer Research 15, ISSUE 1

Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer’s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ‘bird’s-eye view’ of the current state of Alzheimer’s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.


Articles from the journal Current Alzheimer Research 15-1:

For details on the articles, please visit this link: http://bit.ly/2C6iyL4

Highlighted Article – Default Mode Network Connectivity and Related White Matter Disruption in Type 2 Diabetes Mellitus Patients Concurrent with Amnestic Mild Cognitive Impairment – Current Alzheimer Research

CAR-Articles_14-Zhanjun Zhang

To access this article, please visit: http://www.eurekaselect.com/151651

Highlighted Article – A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells – Current Alzheimer Research

car-14-Sourav Kumar

To access this article, please visit: http://www.eurekaselect.com/154200