scholarly journals 3D Mapping of Neurofibrillary Tangle Burden in the Human Medial Temporal Lobe

2021 ◽  
Author(s):  
Paul A Yushkevich ◽  
Mónica Muñoz López ◽  
Maria Mercedes Iñiguez de Onzoño Martin ◽  
Ranjit Ittyerah ◽  
Sydney Lim ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Ex Vivo ◽  
Neurofibrillary Tangle ◽  
Imaging Biomarkers ◽  
Synaptic Loss ◽  
The Brain ◽  
Transentorhinal Region ◽  
Anterior Posterior

Abstract Tau protein neurofibrillary tangles (NFT) are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease (AD) and related dementias. Our knowledge of the pattern of NFT progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in AD, is based on conventional 2D histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe (MTL) specimens were used to construct 3D quantitative maps of NFT burden in the MTL at individual and group levels. These maps reveal significant variation in NFT burden along the anterior-posterior axis. While early NFT pathology is thought to be confined to the transentorhinal region, we find similar levels of NFT burden in this region and other MTL subregions, including amygdala, temporopolar cortex, and subiculum/CA1.

scholarly journals Ex vivo MRI atlas of the human medial temporal lobe: characterizing neurodegeneration due to tau pathology

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sadhana Ravikumar ◽  
Laura E. M. Wisse ◽  
Sydney Lim ◽  
Ranjit Ittyerah ◽  
Long Xie ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Ex Vivo ◽  
Neurofibrillary Tangle ◽  
Stratum Radiatum ◽  
Tau Pathology ◽  
Cornu Ammonis ◽  
Mri Scans ◽  
History Of ◽  
Low Levels

AbstractTau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages.

scholarly journals News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Imaging Techniques ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Specific Proteins ◽  
Great Relevance ◽  
The Brain ◽  
Positive Point

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

scholarly journals A method for single-neuron chronic recording from the retina in awake mice

Science ◽  
2018 ◽  
Vol 360 (6396) ◽  
pp. 1447-1451 ◽  
Author(s):  
Guosong Hong ◽  
Tian-Ming Fu ◽  
Mu Qiao ◽  
Robert D. Viveros ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Single Neuron ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Neural Circuitry ◽  
Retinal Ganglion ◽  
Chronic Recording ◽  
The Brain

The retina, which processes visual information and sends it to the brain, is an excellent model for studying neural circuitry. It has been probed extensively ex vivo but has been refractory to chronic in vivo electrophysiology. We report a nonsurgical method to achieve chronically stable in vivo recordings from single retinal ganglion cells (RGCs) in awake mice. We developed a noncoaxial intravitreal injection scheme in which injected mesh electronics unrolls inside the eye and conformally coats the highly curved retina without compromising normal eye functions. The method allows 16-channel recordings from multiple types of RGCs with stable responses to visual stimuli for at least 2 weeks, and reveals circadian rhythms in RGC responses over multiple day/night cycles.

Ex Vivo Brain Preparation to Analyze Vocal Pathways of Xenopus Frogs

2021 ◽  
Vol 2021 (9) ◽  
pp. pdb.prot106872
Author(s):  
Ayako Yamaguchi
Keyword(s):  
Neural Activity ◽  
Ex Vivo ◽  
Neural Circuitry ◽  
Neural Basis ◽  
Vocal Production ◽  
Basic Principles ◽  
Electrophysiological Recordings ◽  
The Brain

Understanding the neural basis of behavior is a challenging task for technical reasons. Most methods of recording neural activity require animals to be immobilized, but neural activity associated with most behavior cannot be recorded from an anesthetized, immobilized animal. Using amphibians, however, there has been some success in developing in vitro brain preparations that can be used for electrophysiological and anatomical studies. Here, we describe an ex vivo frog brain preparation from which fictive vocalizations (the neural activity that would have produced vocalizations had the brain been attached to the muscle) can be elicited repeatedly. When serotonin is applied to the isolated brains of male and female African clawed frogs, Xenopus laevis, laryngeal nerve activity that is a facsimile of those that underlie sex-specific vocalizations in vivo can be readily recorded. Recently, this preparation was successfully used in other species within the genus including Xenopus tropicalis and Xenopus victorianus. This preparation allows a variety of techniques to be applied including extracellular and intracellular electrophysiological recordings and calcium imaging during vocal production, surgical and pharmacological manipulation of neurons to evaluate their impact on motor output, and tract tracing of the neural circuitry. Thus, the preparation is a powerful tool with which to understand the basic principles that govern the production of coherent and robust motor programs in vertebrates.

scholarly journals Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Pedram Honarpisheh ◽  
Juneyoung Lee ◽  
Anik Banerjee ◽  
Maria P. Blasco-Conesa ◽  
Parisa Honarpisheh ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ex Vivo ◽  
Myeloid Cells ◽  
Amyloid Angiopathy ◽  
Future Studies ◽  
Age Related ◽  
In Vivo Animal Models ◽  
Intermediate Expression ◽  
The Brain

Abstract Background The ability to distinguish resident microglia from infiltrating myeloid cells by flow cytometry-based surface phenotyping is an important technique for examining age-related neuroinflammation. The most commonly used surface markers for the identification of microglia include CD45 (low-intermediate expression), CD11b, Tmem119, and P2RY12. Methods In this study, we examined changes in expression levels of these putative microglia markers in in vivo animal models of stroke, cerebral amyloid angiopathy (CAA), and aging as well as in an ex vivo LPS-induced inflammation model. Results We demonstrate that Tmem119 and P2RY12 expression is evident within both CD45int and CD45high myeloid populations in models of stroke, CAA, and aging. Interestingly, LPS stimulation of FACS-sorted adult microglia suggested that these brain-resident myeloid cells can upregulate CD45 and downregulate Tmem119 and P2RY12, making them indistinguishable from peripherally derived myeloid populations. Importantly, our findings show that these changes in the molecular signatures of microglia can occur without a contribution from the other brain-resident or peripherally sourced immune cells. Conclusion We recommend future studies approach microglia identification by flow cytometry with caution, particularly in the absence of the use of a combination of markers validated for the specific neuroinflammation model of interest. The subpopulation of resident microglia residing within the “infiltrating myeloid” population, albeit small, may be functionally important in maintaining immune vigilance in the brain thus should not be overlooked in neuroimmunological studies.

scholarly journals Automated segmentation of medial temporal lobe subregions on in vivo T1-weighted MRI in early stages of Alzheimer's disease

2019 ◽  
Vol 40 (12) ◽  
pp. 3431-3451 ◽  
Author(s):  
Long Xie ◽  
Laura E. M. Wisse ◽  
John Pluta ◽  
Robin de Flores ◽  
Virgine Piskin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Automated Segmentation ◽  
Early Stages

Antibodies to β-Amyloid Decrease the Blood-to-Brain Transfer of β-Amyloid Peptide1

2002 ◽  
Vol 227 (8) ◽  
pp. 609-615 ◽  
Author(s):  
Weihong Pan ◽  
Beka Solomon ◽  
Lawrence M. Maness ◽  
Abba J. Kastin
Keyword(s):  
Ex Vivo ◽  
Amyloid Β ◽  
Brain Perfusion ◽  
Brain Parenchyma ◽  
Amyloid Angiopathy ◽  
Β Amyloid ◽  
Blocking Antibodies ◽  
The Brain

Amyloid-β peptides (Aβ) play an important role in the pathophysiology of dementia of the Alzheimer's type and in amyloid angiopathy. Aβ outside the CNS could contribute to plaque formation in the brain where its entry would involve interactions with the blood-brain barrier (BBB). Effective antibodies to Aβ have been developed in an effort to vaccinate against Alzheimer's disease. These antibodies could interact with Aβ in the peripheral blood, block the passage of Aβ across the BBB, or prevent Aβ deposition within the CNS. To determine whether the blocking antibodies act at the BBB level, we examined the influx of radiolabeled Aβ (125I-Aβ1-40) into the brain after ex-vivo incubation with the antibodies. Antibody mAb3D6 (élan Company) reduced the blood-to-brain influx of Aβ after iv bolus injection. It also significantly decreased the accumulation of Aβ in brain parenchyma. To confirm the in-vivo study and examine the specificity of mAb3D6, in-situ brain perfusion in serum-free buffer was performed after incubation of 125I-Aβ1-40 with another antibody mAbmc1 (DAKO Company). The presence of mAbmc1 also caused significant reduction of the influx of Aβ into the brain after perfusion. Therefore, effective antibodies to Aβ can reduce the influx of Aβ1-40 into the brain.

Sign in / Sign up

Export Citation Format

Share Document