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Method of diagnosis, prognosis or treatment of neurodegenerative diseases

a neurodegenerative disease and prognostic technology, applied in the field of neurodegenerative diseases diagnosis, prognosis or treatment, can solve the problems of severe debilitating effect on patient's life, disease constitutes an enormous health, social and economic burden, complete erosion of higher cognitive function, etc., to achieve the effect of reducing the level of phosphorylation of protein tau

Inactive Publication Date: 2018-02-15
SORBONNE UNIV +5
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention is a method for diagnosing, prognosticating, and monitoring neurodegenerative diseases such as Alzheimer's disease using a plasma sample that is easier to collect than a CSF sample. The method involves measuring the levels or activity of certain disaccharides, such as a specific degradation product of heparan sulfate and a 3-O-sulfated heparan sulfate disaccharide, which are present in the plasma of patients with Alzheimer's disease. The invention also provides a kit for diagnosis and monitoring of the same diseases using the same disaccharides. Overall, the method and kit offer a reliable and non-invasive tool for identifying individuals at higher risk for neurodegenerative diseases.

Problems solved by technology

Neurodegenerative diseases, in particular Alzheimer's disease (AD), have a strongly debilitating impact on patient's life.
Furthermore, these diseases constitute an enormous health, social, and economic burden.
Clinically, AD is a progressive disease that is associated with early deficits in memory formation and ultimately leads to the complete erosion of higher cognitive function.
Currently, there is no cure for AD, nor is there an effective treatment to halt its progression.
AD ante-mortem diagnosis is still non possible in blood or plasma samples and unfortunately none of the biomarkers presently available in cerebrospinal fluid (CSF) are able to accomplish a differential AD diagnosis from other Tauopathies and in a single-handedly.
It has been suggested that the first consequence of Tau abnormal phosphorylation is its detachment from microtubules, which might result in synapses impairment and cognition decline.
Unfortunately, none of the biomarkers presently available are able to accomplish the disease diagnosis single-handedly and monitoring more than one biomarker at the same time is suggested to be suitable for detecting the disease progression (Anoop et al, International Journal of Alzheimer's Disease 2010).
However, recent notable failures in pivotal clinical trials with agents aimed to reduce the Aβ burden in the brains of patients with Alzheimer's disease, underline the need to pursue other therapeutic approaches, including those that reduce the levels of pathological Tau.

Method used

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  • Method of diagnosis, prognosis or treatment of neurodegenerative diseases
  • Method of diagnosis, prognosis or treatment of neurodegenerative diseases
  • Method of diagnosis, prognosis or treatment of neurodegenerative diseases

Examples

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example 1

sue Dissection from Control and AD Human Brain Tissue

[1014]Post-mortem human brain sampling was performed according to the Consortium to Establish a Registry of AD (CERAD). Two experimental groups were included in the study, an aged group (n=8, control group) with subject ages ranging from 60 to 77 years with a mean of 67.8±2.9 years, and an AD group (n=8) with subjects ages ranging from 69 to 82 years with a mean of 76.8±3.5 years. Subjects included in the study received post-mortem evaluation by a board-certified neuropathologist. Post-mortem intervals varied from 8.0 h to 15.2 h for both groups. No significant statistical difference (p=0.1781) was found for post-mortem delay between the two groups. Brains were obtained at autopsy and halved sagitally within 2 h after autopsy. One hemisphere was cut into 2-cm-thick slabs along the frontal plane from which the hippocampus (temporal lobe), cortex, and cerebellum were dissected. Tissues were immediately frozen after dissection in dry...

example 2

aques and Neurofibrillary Tangles (NFT) Quantification in Control and AD Human Brain Tissue

[1015]Neuropathologic changes in brains were investigated using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and Braak and Braak guidelines. Senile plaques and NFT were determined on Bielschowsky—stained sections of middle frontal gyms, middle temporal gyrus, inferior parietal lobule, occipital pole, hippocampal CA1 and enthorinal cortex. Senile plaques were counted using a 10× objective and NFT were counted with a 20× objective. An arithmetic mean was calculated (Mean±SEM) from the counts of six fields for senile plaques / mm2 and NFT / mm2 for each region. Neuropathologic diagnosis was then made using the guidelines proposed by CERAD and Braak and Braak criteria. AD brains were characterized to be at stage III-V from hippocampal analysis. Control brains were determined to be non AD.

example 3

tochemical HS and Tau Co-Localization on Human Hippocampus

[1016]Sections (20 μm) of human hippocampus from Alzheimer and age-matched control were fixed with 3% acetic acid for 10 min at room temperature (rt). Sections were then incubated for 30 min with 3% BSA dissolved in phosphate-buffered saline (PBS) and permeabilized with 0.2% Triton X100 in PBS for 30 min. HS were stained with an anti-heparan sulfate (10E4 epitope, Seikagaku corp. by AMS Biotechnology) and anti-Tau phosphoSerine 262 (Millipore); dissolved in permeabilization buffer (1:200) and incubated for 1 h 30 min at rt. Fluorescence was introduced by staining tissue slides with a secondary antibody conjugated to an Alexa 568 fluoroprobe (Molecular Probes) and Alexa 488 fluoroprobe (Interchim). Then, sections were DAPI labelled for 3 min with a 1 μg / mL DAPI solution and rinsed with methanol. Images were first obtained using a CCD monochrome camera (CFW-1310M, Scion Corporation, USA) fitted to a BH-2 epi-fluorescence optica...

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Abstract

Methods for the diagnosis and prognosis of neurodegenerative diseases, such as a Tauopathy or Alzheimer's disease, are described. Compositions and methods for the treatment of neurodegenerative diseases are also described.

Description

BACKGROUND OF THE INVENTION[0001]The present invention relates to a method of diagnosis, prognostic or treatment of neurodegenerative diseases, in particular Alzheimer's disease.[0002]Neurodegenerative diseases, in particular Alzheimer's disease (AD), have a strongly debilitating impact on patient's life. Furthermore, these diseases constitute an enormous health, social, and economic burden. AD is the most widespread neurodegenerative disease globally and is estimated to afflict more than 27 million people worldwide. AD accounts for at least 50-70% of all dementia diagnosed clinically and it is probably the most devastating age-related neurodegenerative condition affecting about 10% of the population aver 65 years of age and up to 50% over age 85. The age of onset of AD may vary within a range of 50 years, with early-onset AD occurring in people younger than 65 years of age, and late-onset of AD occurring in those older than 65 years. About 10% of all cases suffer from early-onset A...

Claims

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Application Information

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IPC IPC(8): G01N33/68A61K31/721C12Q1/68C12N15/113A61K31/70G01N33/53A61K31/737A61K31/727A61K31/713A61K38/17
CPCC12N2310/3233A61K31/713G01N2333/91194G01N2440/14G01N2500/20G01N2800/2821A61K31/721G01N2800/52C12N2320/30C12Q1/6883C12Q2600/118C12Q2600/136C12Y208/02023G01N33/6896A61K38/1703A61K31/70A61K38/1709G01N2800/28G01N33/5308C12Q1/686C12Y208/02029C12N2310/14A61K31/737A61K31/727C12Q2600/158C12N15/1137C12Q1/6886G01N2333/47A61P25/28
Inventor PAPY-GARCIA, DULCEHUYNH, MINH BAOSOUSSI-YANICOSTAS, NADIAVOZARI, RITASINERIZ, FERNANDOYANICOSTAS, CONSTANTIN
Owner SORBONNE UNIV