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Detection of alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral schlerosis (ALS), parkinson's disease (PD), and dementia with lewy bodies (DLB) indicated by phosphorylation of marcks

A technology for Alzheimer's disease and frontotemporal lobar degeneration, which can be used in the detection of AD, FTLD, PD and DLB, and in the field of ALS, and can solve problems such as dendritic spine instability and neural degeneration.

Pending Publication Date: 2020-11-03
NAT UNIV CORP TOKYO MEDICAL & DENTAL UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, it has been shown that MARCKS phosphorylation at Ser46 destabilizes dendritic spines and causes neurodegeneration (see Non-Patent Document 2)

Method used

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  • Detection of alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral schlerosis (ALS), parkinson's disease (PD), and dementia with lewy bodies (DLB) indicated by phosphorylation of marcks
  • Detection of alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral schlerosis (ALS), parkinson's disease (PD), and dementia with lewy bodies (DLB) indicated by phosphorylation of marcks
  • Detection of alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral schlerosis (ALS), parkinson's disease (PD), and dementia with lewy bodies (DLB) indicated by phosphorylation of marcks

Examples

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Effect test

Embodiment 1

[0159] [Example 1] Research on Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)

[0160] method

[0161] human patient

[0162] In Nagoya University and Tohoku University, cerebrospinal fluid from 8 AD patients, 7 FTLD patients, and 10 ALS patients were used through neuroimaging diagnosis including clinical symptoms, electrophysiological examination, MRI, SPECT, and PET.

[0163] The control subjects were 6 males (average age 72.6, 55-83 years old) and 4 females (average age 75.5 years, 69-79 years old). Mini-Mental State Examination (MMSE) scores were above 25 (average 28.3, 26-30) at the time point of cerebrospinal fluid (CSF) collection. AD patients were 2 males (54 and 80 years old) and 6 females (average 64.5 years old, 57-75 years old). The MMSE scores of these patients did not exceed 25 (mean 17.1, 4-25), and the mean and range of FAB scores were 9.3 and 6-13. FTLD patients were 5 males and 2 females. The me...

Embodiment 2

[0206] [Example 2] Studies in Parkinson's disease (PD) and dementia with Lewy bodies (DLB)

[0207] method

[0208] Mouse PD / DLB model

[0209] Normal human α-Syn-BAC-Tg mice were produced according to the method described in Yamakado et al (2012) Neurosci Res 73:173-177.

[0210] Specifically, the BAC-Tg construct (containing 28 kb of 5'-flanking sequence and 50 kb of 3'-flanking sequence in addition to PAC AF163864 and BAC AC097478, the entire human gene) was microinjected into C57BL6 / J eggs , homozygous α-Syn-Tg mice were generated. GBA-heterozygous KO mice were purchased from The Jackson Laboratory (B6.129S6-Gbatm1Nsb / J, Stock No. 003321) and crossed with human α-Syn-BAC-Tg mice. The obtained normal human α-Syn-BAC-Tg / GBA-heterozygous-KO (homozygous / heterozygous) mice were maintained as a strain.

[0211] α-Syn-BAC-Tg / GBA-heterozygous-KO mice were bred over 10 generations and used for immunohistochemistry and biological analysis at 1, 6 and 24 months of age (N=3).

[...

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Abstract

Provided is a method for detecting, with high sensitivity and high specificity, neurodegenerative diseases selected from the group consisting of human Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral schlerosis (ALS). A method for detecting neurodegenerative diseases selected from the group consisting of human Alzeimer's disease (AD), frontotemporal lobardegeneration (FTLD), and amyotrophic lateral schlerosis (ALS), the method including the following steps: (i) a step for measuring MARCKS protein phosphorylated on serine 46 in a test specimen collected from a subject, and also measuring non-phosphorylated MARCKS protein; (ii) a step for calculating the DO value represented by Formula 1 from measurement values obtained in step (i) (in the formula,"pSer46-MARCKS" indicates the quantity of MARCKS protein phosphorylated on serine 46, and "non-phosphorylated-MARCKS" indicates the quantity of non-phosphorylated MARCKS protein); and (iii) a step for detecting a neurodegenerative disease using the DO value as an index.

Description

technical field [0001] The invention relates to a detection method for AD (Alzheimer's disease), FTLD (frontotemporal lobar degeneration), ALS (amyotrophic lateral sclerosis), PD (Parkinson's disease) and DLB (dementia with Lewy bodies) . Background technique [0002] The preclinical pathology of neurodegenerative diseases is of great interest, and quantitative biomarkers are needed to measure such early pathology. [0003] Alzheimer's disease (AD) is the most common neurodegenerative disease and a well-known cause of dementia. [0004] One of the most supported models in the etiology of AD is the amyloid hypothesis based on the cytotoxicity of amyloid fibrils produced by the extracellular accumulation of β-amyloid peptide (Aβ). [0005] Based on this hypothesis, Aβ has become a major therapeutic target for AD. Therapeutic strategies, including antibody therapy such as Bapineuzumab and Solanezumab, are to reduce Aβ aggregation in the brain of human AD patients in clinical...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68G01N27/62
CPCG01N33/6896G01N2800/2814G01N2800/2821G01N2800/2835G01N2440/14G01N33/573C12Q1/485
Inventor 冈泽均
Owner NAT UNIV CORP TOKYO MEDICAL & DENTAL UNIV