Alzheimer’s Disease: Characterization of the Brain Sites of the Initial Tau Cytoskeletal Pathology Will Improve the Success of Novel Immunological Anti-Tau Treatment Approaches

2017 ◽  
Vol 57 (3) ◽  
pp. 683-696 ◽  
Author(s):  
Udo Rüb ◽  
Katharina Stratmann ◽  
Helmut Heinsen ◽  
Kay Seidel ◽  
Mohamed Bouzrou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Approaches ◽  
The Brain

scholarly journals EEG Characterization of the Alzheimer’s Disease Continuum by Means of Multiscale Entropies

Entropy ◽  
2019 ◽  
Vol 21 (6) ◽  
pp. 544 ◽  
Author(s):  
Aarón Maturana-Candelas ◽  
Carlos Gómez ◽  
Jesús Poza ◽  
Nadia Pinto ◽  
Roberto Hornero
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Brain Activity ◽  
P Values ◽  
Eeg Data ◽  
High Prevalence ◽  
Average Slope ◽  
The Brain

Alzheimer’s disease (AD) is a neurodegenerative disorder with high prevalence, known for its highly disabling symptoms. The aim of this study was to characterize the alterations in the irregularity and the complexity of the brain activity along the AD continuum. Both irregularity and complexity can be studied applying entropy-based measures throughout multiple temporal scales. In this regard, multiscale sample entropy (MSE) and refined multiscale spectral entropy (rMSSE) were calculated from electroencephalographic (EEG) data. Five minutes of resting-state EEG activity were recorded from 51 healthy controls, 51 mild cognitive impaired (MCI) subjects, 51 mild AD patients (ADMIL), 50 moderate AD patients (ADMOD), and 50 severe AD patients (ADSEV). Our results show statistically significant differences (p-values < 0.05, FDR-corrected Kruskal–Wallis test) between the five groups at each temporal scale. Additionally, average slope values and areas under MSE and rMSSE curves revealed significant changes in complexity mainly for controls vs. MCI, MCI vs. ADMIL and ADMOD vs. ADSEV comparisons (p-values < 0.05, FDR-corrected Mann–Whitney U-test). These findings indicate that MSE and rMSSE reflect the neuronal disturbances associated with the development of dementia, and may contribute to the development of new tools to track the AD progression.

scholarly journals Immunocytochemical Characterization of Alzheimer’s Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-β Vaccine

2014 ◽  
Vol 2 ◽  
Author(s):  
Ivan Carrera ◽  
Ignacio Etcheverria ◽  
Yi Li ◽  
Lucia Fernandez-Novoa ◽  
Valter Lombardi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Inflammatory Responses ◽  
Passive Immunization ◽  
New Approach ◽  
Double Transgenic Mouse ◽  
Sphingosine 1 Phosphate ◽  
The Brain

Introduction: APP/PS1 double-transgenic mouse models of Alzheimer’s disease (AD), which overexpress mutated forms of the gene for the human amyloid precursor protein (APP) and presenilin 1 (PS1), have provided robust neuropathological hallmarks of an AD-like pattern at early ages. This study aimed to characterize immunocytochemical patterns of the AD mouse brain, which is treated with the EB101 vaccine, as a model for human AD.Material and methods: In this novel vaccine, a new approach has been taken to circumvent past failures with Aβ vaccines by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol).Results: Our findings showed that the administration of amyloid-β1−42 (Aβ) and sphingosine-1-phosphate emulsified in liposome complex (EB101) to APP/PS1 mice before the onset of Aβ brain deposition (at 7 weeks of age) and/or at an older age (35 weeks of age) can be effective in both halting the progression and clearing the AD-like neuropathological hallmarks. In addition, passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus) in the brain of treated mice was notably reduced.Conclusion: These results provide strong evidence that immunization with the EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.

scholarly journals Noninvasive characterization of Alzheimer’s disease by circulating, cell-free messenger RNA next-generation sequencing

2020 ◽  
Vol 6 (50) ◽  
pp. eabb1654
Author(s):  
Shusuke Toden ◽  
Jiali Zhuang ◽  
Alexander D. Acosta ◽  
Amy P. Karns ◽  
Neeraj S. Salathia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Messenger Rna ◽  
Biological Processes ◽  
Molecular Alterations ◽  
Gene Transcripts ◽  
Noninvasive Characterization ◽  
The Brain ◽  
Generation Sequencing

The lack of accessible noninvasive tools to examine the molecular alterations occurring in the brain limits our understanding of the causes and progression of Alzheimer’s disease (AD), as well as the identification of effective therapeutic strategies. Here, we conducted a comprehensive profiling of circulating, cell-free messenger RNA (cf-mRNA) in plasma of 126 patients with AD and 116 healthy controls of similar age. We identified 2591 dysregulated genes in the cf-mRNA of patients with AD, which are enriched in biological processes well known to be associated with AD. Dysregulated genes included brain-specific genes and resembled those identified to be dysregulated in postmortem AD brain tissue. Furthermore, we identified disease-relevant circulating gene transcripts that correlated with the severity of cognitive impairment. These data highlight the potential of high-throughput cf-mRNA sequencing to evaluate AD-related pathophysiological alterations in the brain, leading to precision healthcare solutions that could improve AD patient management.

scholarly journals Sex Differences in the Neuropsychiatric Symptoms of Patients With Alzheimer’s Disease

2018 ◽  
Vol 33 (7) ◽  
pp. 450-457 ◽  
Author(s):  
Ye Tao ◽  
Matthew E. Peters ◽  
Lea T. Drye ◽  
Davangere P. Devanand ◽  
Jacobo E. Mintzer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Rating Scale ◽  
Clinical Presentation ◽  
Neuropsychiatric Symptoms ◽  
Multicenter Trial ◽  
Neuropsychiatric Inventory ◽  
Treatment Approaches

The aim of this study was to describe sex differences in neuropsychiatric symptoms (NPSs) in patients with Alzheimer’s disease (AD). Baseline scores on the Cohen-Mansfield Agitation Inventory, Neurobehavioral Rating Scale–Agitation subscale, and the Neuropsychiatric Inventory from patients with AD enrolled in a multicenter trial of citalopram for the treatment of agitation were analyzed. We found not only that patients with AD having agitation were likely to exhibit many other NPSs but also that the women in this study were more likely to exhibit a broader range of NPS than were the men. These results suggest greater heterogeneity in the clinical presentation of women compared to men, and thus in the potential targets for treatment in these patients. Further characterization of sex differences in NPS can inform future efforts aimed at establishing subtypes of patients for whom various treatment approaches will be most appropriate.

scholarly journals Characterization of Tau ELISAs for Evaluating Tau Accumulation in the Brains With Alzheimer’s Disease

2021 ◽  
Author(s):  
Mitsuru Shinohara ◽  
Junko Hirokawa ◽  
Akemi Shimodaira ◽  
Yoshitaka Tashiro ◽  
Kaoru Suzuki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Regions ◽  
The Other ◽  
Disease Stage ◽  
Brain Areas ◽  
Biochemical Level ◽  
The Brain ◽  
Control Samples

Abstract Background: One main pathological hallmark of Alzheimer’s disease (AD) is tau accumulation as neurofibrillary tangles (NFTs) in the brain. Although sandwich enzyme-linked immunosorbent assays (ELISAs) are useful for quantifying tau levels, including those in CSF, plasma and brain, it has not yet been determined which antibody combination is the most appropriate for assessing the neuropathological accumulation of tau in the brain. Methods: We developed several sandwich tau ELISAs by introducing antibodies against several tau epitopes, including from its N-terminal and C-terminal regions, and evaluated tau levels depending on disease stage, brain areas, and other AD-related changes. Results: We observed that tau levels in insoluble brain fraction determined by each ELISAs differ depending on the epitopes of the antibodies: there is a trend that non-AD control samples yield relatively high signals when an antibody against the N-terminal region of tau is used. On the other hand, ELISAs combining two antibodies against the later-middle to C-terminal regions of tau produced substantially increased signals from AD samples, compared to those from non-AD controls. Such ELISAs better distinguish AD and non-AD controls, and the results are more closely associated with Braak NFT stage, Aβ accumulation, and neuroinflammatory markers. In addition, these ELISAs can reflect the pattern of tau spread across brain regions. Conclusions: Tau ELISAs that combine two antibodies against the later-middle to C-terminal regions of tau can better reflect neuropathological tau accumulation, which would enable to evaluate tau accumulation in the brain at a biochemical level.

P1-163: Functional and Pathological Characterization of the Brain Microvasculature in a Rat Model of Alzheimer's Disease

2016 ◽  
Vol 12 ◽  
pp. P465-P465
Author(s):  
Lewis I. Joo ◽  
Aaron Y. Lai ◽  
John G. Sled ◽  
JoAnne McLaurin ◽  
Bojana Stefanovic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Model Of Alzheimer’S Disease ◽  
Brain Microvasculature ◽  
The Brain

Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽  
2012 ◽  
Vol 25 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Katja Franke ◽  
Christian Gaser
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Elderly Subjects ◽  
Additional Increase ◽  
Longitudinal Changes ◽  
Novel Method ◽  
The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

The Weak Combined Magnetic Fields Reduce the Brain β-Amyloid in an Animal Model of Sporadic Alzheimer's Disease

PIERS Online ◽  
2009 ◽  
Vol 5 (4) ◽  
pp. 311-315 ◽  
Author(s):  
Natalia V. Bobkova ◽  
Vadim V. Novikov ◽  
Natalia I. Medvinskaya ◽  
Irina Yu. Aleksandrova ◽  
Eugenii E. Fesenko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Magnetic Fields ◽  
Sporadic Alzheimer’S Disease ◽  
Combined Magnetic Fields ◽  
The Brain

SPECIFIC PROPERTIES OF TUBULIN IN THE PREFRONTAL CORTEX IN CONTROL, SCHIZOPHRENIA AND VASCULAR DEMENTIA

2020 ◽  
pp. 65-71
Author(s):  
Burbaeva G.Sh. ◽  
Androsova L.V. ◽  
Vorobyeva E.A. ◽  
Savushkina O.K.
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Vascular Dementia ◽  
Binding Activity ◽  
Nephelometric Method ◽  
Rate Of Polymerization ◽  
Mental Diseases ◽  
And Control ◽  
The Brain

The aim of the study was to evaluate the rate of polymerization of tubulin into microtubules and determine the level of colchicine binding (colchicine-binding activity of tubulin) in the prefrontal cortex in schizophrenia, vascular dementia (VD) and control. Colchicine-binding activity of tubulin was determined by Sherlinе in tubulin-enriched extracts of proteins from the samples. Measurement of light scattering during the polymerization of the tubulin was carried out using the nephelometric method at a wavelength of 450-550 nm. There was a significant decrease in colchicine-binding activity and the rate of tubulin polymerization in the prefrontal cortex in both diseases, and in VD to a greater extent than in schizophrenia. The obtained results suggest that not only in Alzheimer's disease, but also in other mental diseases such as schizophrenia and VD, there is a decrease in the level of tubulin in the prefrontal cortex of the brain, although to a lesser extent than in Alzheimer's disease, and consequently the amount of microtubules.

The Therapeutic Potential of Purinergic Receptors in Alzheimer’s Disease and Promising Therapeutic Modulators

2020 ◽  
Vol 20 ◽  
Author(s):  
Lili Pan ◽  
Yu Ma ◽  
Yunchun Li ◽  
Haoxing Wu ◽  
Rui Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Purinergic Receptors ◽  
Therapeutic Potential ◽  
Purinergic Signaling ◽  
Memory Loss ◽  
Related Research ◽  
Central Nervous System Disorders ◽  
G Protein Coupled

Abstract:: Recent studies have proven that the purinergic signaling pathway plays a key role in neurotransmission and neuromodulation, and is involved in various neurodegenerative diseases and psychiatric disorders. With the characterization of the subtypes of receptors in purinergic signaling, i.e. the P1 (adenosine), P2X (ion channel) and P2Y (G protein-coupled), more attentions were paid to the pathophysiology and therapeutic potential of purinergic signaling in central nervous system disorders. Alzheimer’s disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. However, as drug development aimed to prevent or control AD follows a series of failures in recent years, more researchers focused on the neuroprotection-related mechanisms such as purinergic signaling in AD patients to find a potential cure. This article reviews the recent discoveries of purinergic signaling in AD, summaries the potential agents as modulators for the receptors of purinergic signaling in AD related research and treatments. Thus, our paper provided an insight for purinergic signaling in the development of anti-AD therapies.

Sign in / Sign up

Export Citation Format

Share Document