Correlation between senile plaque and neurofibrillary tangle counts in cerebral cortex and neuronal counts in cortex and subcortical structures in Alzheimer's disease

1985 ◽  
Vol 56 (1) ◽  
pp. 51-55 ◽  
Author(s):  
David M.A. Mann ◽  
Peter O. Yates ◽  
Borys Marcyniuk
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Cortex ◽  
Senile Plaque ◽  
Neurofibrillary Tangle ◽  
Subcortical Structures

scholarly journals Vaccine Development to Treat Alzheimer’s Disease Neuropathology in APP/PS1 Transgenic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Iván Carrera ◽  
Ignacio Etcheverría ◽  
Lucía Fernández-Novoa ◽  
Valter Lombardi ◽  
Ramón Cacabelos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
T Cell Activation ◽  
Cell Activation ◽  
Vaccine Development ◽  
Senile Plaque ◽  
Neurofibrillary Tangle ◽  
Plaque Burden ◽  
Activation Markers

A novel vaccine addressing the major hallmarks of Alzheimer’s disease (AD), senile plaque-like deposits of amyloid beta-protein (Aβ), neurofibrillary tangle-like structures, and glial proinflammatory cytokines, has been developed. The present vaccine takes a new approach to circumvent failures of previous ones tested in mice and humans, including the Elan-Wyeth vaccine (AN1792), which caused massive T-cell activation, resulting in a meningoencephalitis-like reaction. The EB101 vaccine consists ofAβ1-42delivered in a novel immunogen-adjuvant composed of liposomes-containing sphingosine-1-phosphate (S1P). EB101 was administered to APPswe/PS1dE9 transgenic mice before and after AD-like pathological symptoms were detectable. Treatment with EB101 results in a marked reduction of Aβplaque burden, decrease of neurofibrillary tangle-like structure density, and attenuation of astrocytosis. In this transgenic mouse model, EB101 reduces the basal immunological interaction between the T cells and immune activation markers in the affected hippocampal/cortical areas, consistent with decreased amyloidosis-induced inflammation. Therefore, immunization with EB101 prevents and reverses AD-like neuropathology in a significant manner by halting disease progression without developing behavioral spatial deficits in transgenic mice.

scholarly journals Donor specific transcriptomic analysis of Alzheimer’s disease associated hypometabolism highlights a unique donor, microglia, and ribosomal proteins

2019 ◽  
Author(s):  
Sejal Patel ◽  
Derek Howard ◽  
Alana Man ◽  
Deborah Schwartz ◽  
Joelle Jee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Cortex ◽  
Glucose Utilization ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Neurofibrillary Tangle ◽  
Brain Atlas ◽  
Angular Gyrus ◽  
Healthy Controls

AbstractAlzheimer’s disease (AD) starts decades before clinical symptoms appear. Low glucose utilization in regions of the cerebral cortex marks early AD and is clinically useful. To identify these regions, we conducted a voxel-wise meta-analysis of positron emission tomography studies that compared AD patients with healthy controls. This meta-analysis included 27 studies that assayed glucose utilization in 915 AD patients and 715 healthy controls. The resulting map marks hypometabolism in the posterior cingulate, middle frontal, angular gyrus, middle and inferior temporal regions. Using the Allen Human Brain Atlas, we identified genes with expression patterns associated with this hypometabolism pattern in the cerebral cortex. Of the six brains in the Atlas, one demonstrated a strong spatial association with the hypometabolism pattern. Previous neuropathological assessment of this brain from a 39-year-old male noted a neurofibrillary tangle in the entorhinal cortex. Using the transcriptomic data, we estimate lower proportions of neurons and more microglia in the hypometabolic regions when compared with the other five brains. Within this single brain, signal recognition particle (SRP)-dependent cotranslational protein targeting genes, which primarily encode cytosolic ribosome proteins, are highly expressed in the hypometabolic regions. Analyses of human and mouse data show that expression of these genes progressively increases across AD-associated states of microglial activation. In addition, genes involved in cell killing, chronic inflammation, ubiquitination, tRNA aminoacylation, and vacuole sorting are associated with the hypometabolism map. These genes suggest disruption of the protein life cycle and neuroimmune activation. Taken together, our molecular characterization of cortical hypometabolism reveals a molecular link to AD associated hypometabolism that may be relevant to preclinical stages.

scholarly journals Amyloid-beta peptide and phosphorylated tau in the frontopolar cerebral cortex and in the cerebellum of toothed whales: aging vs hypoxia

2020 ◽  
Author(s):  
Simona Sacchini ◽  
Josué Díaz ◽  
Antonio Espinosa de los Monteros ◽  
Yania Paz ◽  
Yara Bernaldo de Quirós ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Cortex ◽  
Neurodegenerative Diseases ◽  
Cortical Neurons ◽  
Neurofibrillary Tangle ◽  
Immunohistochemical Analysis ◽  
Granulovacuolar Degeneration ◽  
Beaked Whales ◽  
The Brain

Abstract Background: Alzheimer’s disease results from the interplay of multiple risk factors and their effects. Diving mammals may be routinely exposed to severe hypoxia when submerged. Among toothed whales, the beaked whales are particularly cryptic and routinely dive deeper than 1,000 m for about one hour in order to hunt deep-water squid and fish. We hypothesized that hypoxia could be a possible risk factor for neurodegenerative alterations in the central nervous system of beaked whales in particular, and toothed whales in general. Results: Samples of frontal cerebral cortex and cerebellum were collected from nine animals, representing six different species of the suborder Odontoceti. Immunohistochemical analysis employed a monoclonal anti-β-amyloid (Aβ) and a polyclonal anti-neurofibrillary tangle (NFT) antibodies. Six of nine (67%) animals showed positive immunolabeling for Aβ and/or NFT. The most striking findings were intranuclear Aβ immunopositivity in cerebral cortical neurons and NFT immunopositivity in cerebellar Purkinje neurons with granulovacuolar degeneration. Herein, we present immunohistopathological findings classic of Alzheimer’s and other neurodegenerative diseases in humans, in different brain locales of odontocete cetaceans. This study represents the first description of Aβ and NFT in the brain of beaked whales, adding also to the non-existent descriptions of GVD in the brain of non-experimental animals, being specifically the first report of granulovacuolar degeneration in the cerebellum. Our results further confirm the rarely reported intranuclear expression of Aβ. Conclusions: These findings could be linked to hypoxic phenomena, as they were more extensive in the brains of beaked whales, and not only in aged individuals. Therefore, a novel hypothesis linking hypoxia and neurodegeneration microscopic hallmarks in cetaceans is proposed. Despite their adaptations, diving mammals could be vulnerable to sustained and repetitive brain hypoxia. Future comparative pathological and neuroprotective investigations may prove of great value to Alzheimer’s disease and other neurodegenerative diseases in humans.

scholarly journals Applying fluid biomarkers to Alzheimer's disease

2017 ◽  
Vol 313 (1) ◽  
pp. C3-C10 ◽  
Author(s):  
Henrik Zetterberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Clinical Symptoms ◽  
Senile Plaque ◽  
Neurofibrillary Tangle ◽  
Amyloid Β ◽  
Differential Diagnoses ◽  
Blood Tests ◽  
The Brain

Alzheimer’s disease (AD) is a common neurodegenerative disease that starts with a clinically silent phase of a decade or more during which brain pathologies accumulate predominantly in the medial temporal lobe but also elsewhere in the brain. Network dysfunction and clinical symptoms typically appear when senile plaque (amyloid-β) and neurofibrillary tangle (tau) pathologies meet in the brain parenchyma, producing synapse and neuronal loss. For plaque and tangle pathologies, reliable fluid biomarkers have been developed. These require sampling of cerebrospinal fluid. Reliable blood tests for plaque and tangle pathologies are currently lacking, but blood tests for general neurodegeneration have recently been developed. In AD, plaques and tangles often coexist with other pathologies, including Lewy bodies, and to what extent these contribute to symptoms is currently unknown. There are also important differential diagnoses that may be possible to distinguish from AD with the aid of biomarkers. The scope of this review is fluid biomarkers for AD and related pathologies. The purpose is to provide the reader with an updated account of currently available fluid biomarkers for AD and clinically relevant differential diagnoses.

Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Protein Level ◽  
Senile Plaque ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

Biological Signatures of Alzheimer’s Disease

2020 ◽  
Vol 20 (9) ◽  
pp. 770-781 ◽  
Author(s):  
Poornima Sharma ◽  
Anjali Sharma ◽  
Faizana Fayaz ◽  
Sharad Wakode ◽  
Faheem H. Pottoo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Senile Plaque ◽  
Senile Plaques ◽  
Amyloid Deposition ◽  
Immune Defense ◽  
Amyloid Angiopathy ◽  
Microvascular Changes ◽  
Β Amyloid

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

scholarly journals Senile plaque calcification of the lamina circumvoluta medullaris in Alzheimer's disease

2021 ◽  
Author(s):  
Ralf Schober ◽  
Isabel Hilbrich ◽  
Carsten Jäger ◽  
Max Holzer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaque

scholarly journals Disruption of a RAC1-centred network is associated with Alzheimer’s disease pathology and causes age-dependent neurodegeneration

2020 ◽  
Vol 29 (5) ◽  
pp. 817-833 ◽  
Author(s):  
Masataka Kikuchi ◽  
Michiko Sekiya ◽  
Norikazu Hara ◽  
Akinori Miyashita ◽  
Ryozo Kuwano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Model ◽  
Neurofibrillary Tangle ◽  
Neuronal Cell ◽  
Brain Regions ◽  
Protein Domain ◽  
Expression Data ◽  
Integrated Network ◽  
Age Dependent

Abstract The molecular biological mechanisms of Alzheimer’s disease (AD) involve disease-associated crosstalk through many genes and include a loss of normal as well as a gain of abnormal interactions among genes. A protein domain network (PDN) is a collection of physical bindings that occur between protein domains, and the states of the PDNs in patients with AD are likely to be perturbed compared to those in normal healthy individuals. To identify PDN changes that cause neurodegeneration, we analysed the PDNs that occur among genes co-expressed in each of three brain regions at each stage of AD. Our analysis revealed that the PDNs collapsed with the progression of AD stage and identified five hub genes, including Rac1, as key players in PDN collapse. Using publicly available as well as our own gene expression data, we confirmed that the mRNA expression level of the RAC1 gene was downregulated in the entorhinal cortex (EC) of AD brains. To test the causality of these changes in neurodegeneration, we utilized Drosophila as a genetic model and found that modest knockdown of Rac1 in neurons was sufficient to cause age-dependent behavioural deficits and neurodegeneration. Finally, we identified a microRNA, hsa-miR-101-3p, as a potential regulator of RAC1 in AD brains. As the Braak neurofibrillary tangle (NFT) stage progressed, the expression levels of hsa-miR-101-3p were increased specifically in the EC. Furthermore, overexpression of hsa-miR-101-3p in the human neuronal cell line SH-SY5Y caused RAC1 downregulation. These results highlight the utility of our integrated network approach for identifying causal changes leading to neurodegeneration in AD.

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