ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease

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

Abstract Despite the routine use of sandwich enzyme-linked immunosorbent assays (ELISAs) for quantifying tau levels in CSF and plasma, tau accumulations in the brains of patients with Alzheimer disease (AD) have rarely been evaluated by this method. Thus, by introducing several tau ELISAs that target different epitopes, we evaluated accumulated tau levels in postmortem brains depending on disease stage, brain areas, and other AD-related changes. Notably, tau levels in insoluble fraction determined by each ELISAs differ depending on the epitopes of antibodies: 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 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 neurofibrillary tangles stage, Aβ accumulation, and glial markers. Moreover, these ELISAs can reflect the pattern of tau spread across brain regions. In conclusion, Tau ELISAs that combine 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.

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.

Differential recovery of acetylcholinesterase in guinea pig muscle and brain regions after soman treatment

1998 ◽  
Vol 17 (3) ◽  
pp. 157-162 ◽  
Author(s):  
Maxine C Lintern ◽  
Janet R Wetherell ◽  
Margaret E Smith
Keyword(s):  
Enzyme Activity ◽  
Time Course ◽  
Brain Regions ◽  
Similar Rate ◽  
Molecular Forms ◽  
Similar Degree ◽  
Brain Areas ◽  
Pig Muscle ◽  
Rate Of Recovery ◽  
The Brain

1 In brain areas of untreated guinea-pigs the highest activity of acetylcholinesterase was seen in the striatum and cerebellum, followed by the midbrain, medulla-pons and cortex, and the lowest in the hippocampus. The activity in diaphragm was sevenfold lower than in the hippocampus. 2 At 1 h after soman (27 mg/kg) administration the activity of the enzyme was dramatically reduced in all tissues studied. In muscle the three major molecular forms (A12, G4 and G1) showed a similar degree of inhibition and a similar rate of recovery and the activity had returned to normal by 7 days. 3 In the brain soman inhibited the G4 form more than the G1 form. The hippocampus, cortex and midbrain showed the greatest reductions in enzyme activity. At 7 days the activity in the cortex, medulla pons and striatum had recovered but in the hippocampus, midbrain and cerebellum it was still inhibited. 4 Thus the effects of soman administration varied in severity and time course in the different tissues studied. However the enzyme activity was still reduced in all tissues at 24 h when the overt signs of poisoning had disappeared.

scholarly journals Recent developments in cognitive fMRI for temporal lobe epilepsy

2019 ◽  
Vol 33 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Victor Schmidbauer ◽  
Silvia Bonelli
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Visual Memory ◽  
Imaging Modality ◽  
Memory Function ◽  
Brain Regions ◽  
Epileptogenic Zone ◽  
Brain Areas ◽  
Recent Developments ◽  
The Brain

AbstractEpilepsy is frequently accompanied by severe cognitive side effects. Temporal lobe epilepsy (TLE), and even successful surgical treatment, may affect cognitive function, in particular language as well as verbal and visual memory function. Epilepsy arising from the temporal lobe can be controlled surgically in up to 70% of patients. The goals of epilepsy surgery are to remove the brain areas generating the seizures without causing or aggravating neuropsychological deficits. This requires accurate localization of the brain areas generating the seizures (“epileptogenic zone”) and the areas responsible for motor and cognitive functions, such as language and memory (“essential brain regions”) during presurgical evaluation. In the past decades, functional magnetic resonance imaging (fMRI) has been increasingly used to noninvasively lateralize and localize not only primary motor and somatosensory areas, but also brain areas that are involved in everyday language and memory processes. The imaging modality also shows potential for predicting the effects of temporal lobe resection on language and memory function. Together with other MRI modalities, cognitive fMRI is a promising tool to improve surgical strategies tailored to individual patients with regard to functional outcome, by virtue of definition of epileptic cerebral areas that need to be resected and eloquent areas that need to be spared.The aim of this review is to provide an overview of recent developments and practical recommendations for the clinical use of cognitive fMRI in TLE.

Music, Maestro, Please: Thalamic multisensory integration in music perception, processing and production

2019 ◽  
Vol 11 (2) ◽  
pp. 98
Author(s):  
Artur Jaschke
Keyword(s):  
Multisensory Integration ◽  
Music Perception ◽  
Initial Point ◽  
Initial Step ◽  
Brain Regions ◽  
Thalamic Nuclei ◽  
Brain Areas ◽  
Neural Connections ◽  
Parietal Lobes ◽  
The Brain

Music activates a wide array of brain areas involved in different functions such as   perception, processing and execution of music. Understanding musical processes in the brain has multiple implications in the neuro- and health sciences.  Challenging the brain with a multisensory stimulus such as music activates responses beyond the auditory cortex of the temporal lobe. Other areas that are involved include the frontal lobes, parietal lobes, areas of the limbic system such as the amygdala, hippocampus and thalamus, the cerebellum and the brainstem. Nonetheless, there has been no attempt to summarize all involved brain areas in music into one overall encompassing map. This may well be, as there has been no thorough theory introduced, which would allow an initial point of departure in creating such a mapTherefore, a thorough systematic review has been conducted to identify all mentioned neural connections involved in the perception, processing and execution of music.  Communication between the thalamic nuclei is the initial step in multisensory integration, which lies at the base of the neural networks as proposed in this paper. Against this background, this manuscript introduces the to our knowledge first map of all brain regions involved in the perception, processing and execution of music.Consequently, placing thalamic multisensory integration at the core of this atlas allowed us to create a preliminary theory to explain the complexity of music induced brain activation.

scholarly journals A Core Set of Brain Regions Helps Kids Achieve Their Goals

2021 ◽  
Vol 9 ◽  
Author(s):  
AnnaCarolina Garza ◽  
Alice Aizza ◽  
Janchira K. Charoenworawat ◽  
Jessica A. Church
Keyword(s):  
Young People ◽  
Executive Functions ◽  
Brain Regions ◽  
Simple Games ◽  
Brain Areas ◽  
Core Set ◽  
The Brain

Your brain is always adjusting to the changing swirl of activities and interactions you have every day. Every time you accomplish a goal, you are exercising what are called the brain’s executive functions. These skills include resisting impulses, switching between tasks, and updating information in your memory. We asked whether these different skills relied on the same brain areas, and whether young people used the same brain areas as adults. We took pictures of kids’ and teens’ brains to see which areas of the brain they were using while they played three simple games related to these executive functions. We found that youth used similar brain regions to adults while playing the three games, and that many parts of the brain were used across all three games. These results help us understand how kids use their brains to be successful and how these skills develop.

scholarly journals Imbalanced Dopaminergic Transmission Mediated by Serotonergic Neurons in L-DOPA-Induced Dyskinesia

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Sylvia Navailles ◽  
Philippe De Deurwaerdère
Keyword(s):  
Brain Regions ◽  
Term Treatment ◽  
Serotonergic Neurons ◽  
Brain Areas ◽  
Dopaminergic Transmission ◽  
The Core ◽  
Long Term Treatment ◽  
The Brain ◽  
Serotonergic Innervation

L-DOPA-induced dyskinesias (LIDs) are one of the main motor side effects of L-DOPA therapy in Parkinson's disease. The review will consider the biochemical evidence indicating that the serotonergic neurons are involved in the dopaminergic effects of L-DOPA in the brain. The consequences are an ectopic and aberrant release of dopamine that follows the serotonergic innervation of the brain. After mid- to long-term treatment with L-DOPA, the pattern of L-DOPA-induced dopamine release is modified. In several brain regions, its effect is dramatically reduced while, in the striatum, its effect is quite preserved. LIDs could appear when the dopaminergic effects of L-DOPA fall in brain areas such as the cortex, enhancing the subcortical impact of dopamine and promoting aberrant motor responses. The consideration of the serotonergic system in the core mechanism of action of L-DOPA opens an important reserve of possible strategies to limit LIDs.

scholarly journals Hierarchy in sensory processing reflected by innervation balance on cortical interneurons

2021 ◽  
Vol 7 (20) ◽  
pp. eabf5676
Author(s):  
Guofen Ma ◽  
Yanmei Liu ◽  
Lizhao Wang ◽  
Zhongyi Xiao ◽  
Kun Song ◽  
...  
Keyword(s):  
Long Range ◽  
Sensory Processing ◽  
Visual Processing ◽  
Brain Regions ◽  
Brain Areas ◽  
Local Interneurons ◽  
Cortical Interneurons ◽  
Different Types ◽  
Virus Tracing ◽  
The Brain

Sensory processing is subjected to modulation by behavioral contexts that are often mediated by long-range inputs to cortical interneurons, but their selectivity to different types of interneurons remains largely unknown. Using rabies-virus tracing and optogenetics-assisted recording, we analyzed the long-range connections to various brain regions along the hierarchy of visual processing, including primary visual cortex, medial association cortices, and frontal cortices. We found that hierarchical corticocortical and thalamocortical connectivity is reflected by the relative weights of inputs to parvalbumin-positive (PV+) and vasoactive intestinal peptide–positive (VIP+) neurons within the conserved local circuit motif, with bottom-up and top-down inputs preferring PV+ and VIP+ neurons, respectively. Our algorithms based on innervation weights for these two types of local interneurons generated testable predictions of the hierarchical position of many brain areas. These results support the notion that preferential long-range inputs to specific local interneurons are essential for the hierarchical information flow in the brain.

scholarly journals Beat Detection Recruits the Visual Cortex in Early Blind Subjects

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 296
Author(s):  
Rodrigo Araneda ◽  
Sandra Silva Moura ◽  
Laurence Dricot ◽  
Anne G. De Volder
Keyword(s):  
Brain Plasticity ◽  
Brain Activity ◽  
Sensory Modality ◽  
Brain Regions ◽  
Rhythm Perception ◽  
Brain Areas ◽  
Sensory Modalities ◽  
Beat Detection ◽  
The Brain ◽  
Early Blindness

Using functional magnetic resonance imaging, here we monitored the brain activity in 12 early blind subjects and 12 blindfolded control subjects, matched for age, gender and musical experience, during a beat detection task. Subjects were required to discriminate regular (“beat”) from irregular (“no beat”) rhythmic sequences composed of sounds or vibrotactile stimulations. In both sensory modalities, the brain activity differences between the two groups involved heteromodal brain regions including parietal and frontal cortical areas and occipital brain areas, that were recruited in the early blind group only. Accordingly, early blindness induced brain plasticity changes in the cerebral pathways involved in rhythm perception, with a participation of the visually deprived occipital brain areas whatever the sensory modality for input. We conclude that the visually deprived cortex switches its input modality from vision to audition and vibrotactile sense to perform this temporal processing task, supporting the concept of a metamodal, multisensory organization of this cortex.

scholarly journals Communicability distance reveals hidden patterns of Alzheimer disease

2020 ◽  
Author(s):  
Eufemia Lella ◽  
Ernesto Estrada
Keyword(s):  
Alzheimer Disease ◽  
Path Length ◽  
Brain Regions ◽  
Brain Network ◽  
Efficient System ◽  
Brain Hemispheres ◽  
Disconnection Syndrome ◽  
Path Lengths ◽  
The Brain ◽  
Better Than

AbstractThe communicability distance between pairs of regions in human brain is used as a quantitative proxy for studying Alzheimer disease. Using this distance we obtain the shortest communicability path lengths between different regions of brain networks from Alzheimer diseased (AD) patients and healthy cohorts (HC). We show that the shortest communicability path length is significantly better than the shortest topological path length in distinguishing AD patients from HC. Based on this approach we identify 399 pairs of brain regions for which there are very significant changes in the shortest communicability path length after AD appears. We find that 42% of these regions interconnect both brain hemispheres, 28% connect regions inside the left hemisphere only and 20% affects vermis connection with brain hemispheres. These findings clearly agree with the disconnection syndrome hypothesis of Alzheimer disease. Finally, we show that in 76.9% damaged brain regions the shortest communicability path length drops in AD in relation to HC. This counterintuitive finding indicates that AD transforms the brain network into a more efficient system from the perspective of the transmission of the disease, because it drops the circulability of the disease factor around the brain regions in relation to its transmissibility to other regions.

scholarly journals Processing of a spoken narrative in the human brain is shaped by family cultural background

2020 ◽  
Author(s):  
M. Hakonen ◽  
A. Ikäheimonen ◽  
A. Hultèn ◽  
J. Kauttonen ◽  
M. Koskinen ◽  
...  
Keyword(s):  
Social Identity ◽  
Human Brain ◽  
Native Speakers ◽  
Family Background ◽  
Cultural Background ◽  
The Other ◽  
Mutual Understanding ◽  
Brain Areas ◽  
Narrative Processing ◽  
The Brain

ABSTRACTUsing neuroimaging, we studied influence of family cultural background on processing of an audiobook in human brain. The audiobook depicted life of two young Finnish men, one with the Finnish and the other with the Russian family background. Shared family cultural background enhanced similarity of narrative processing in the brain at prelexical, word, sentence, and narrative levels. Similarity was also enhanced in brain areas supporting imagery. The cultural background was further reflected as semantic differences in word lists by which the subjects described what had been on their minds when they heard the audiobook during neuroimaging. Strength of social identity shaped word, sentence, and narrative level processing in the brain. These effects might enhance mutual understanding between persons who share family cultural background and social identity and, conversely, deteriorate between-group mutual understanding in modern multicultural societies wherein native speakers of a language may assume highly similar understanding.

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