WO1992006376A1 - PROCEDE DE DETECTION DE LA PROTEINE β-AMYLOIDE PAR LIAISON NON SPECIFIQUE D'OLIGONUCLEOTIDES - Google Patents
PROCEDE DE DETECTION DE LA PROTEINE β-AMYLOIDE PAR LIAISON NON SPECIFIQUE D'OLIGONUCLEOTIDES Download PDFInfo
- Publication number
- WO1992006376A1 WO1992006376A1 PCT/FI1991/000300 FI9100300W WO9206376A1 WO 1992006376 A1 WO1992006376 A1 WO 1992006376A1 FI 9100300 W FI9100300 W FI 9100300W WO 9206376 A1 WO9206376 A1 WO 9206376A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- amyloid
- oligonucleotides
- amyloid protein
- precursor
- detection
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2821—Alzheimer
Definitions
- the invention relates to the detection of proteins by means of oligonucleotides.
- the invention may be utilized especially in diagnostics.
- Alzheimer's disease is a disease resulting in a difficult dementia, in which the risk of falling ill increases along with aging. Symptoms of Alzheimer's disease are the progressive deterioration of memory, perception and other higher brain functions, which finally results in the patient's complete feeblemindedness.
- the pathological changes caused by it are fairly well-known.
- the most typical changes are the extracellular accumulation of amyloid protein on the walls of the cerebral membranes and blood vessels as well as as senile plaques.
- the cyto-skelenton components of neurons aggregate intracellularly as so-called neurofi- brillary tangles.
- the filamentary proteins may completely change the structure of the neuron, which finally results in the dystrophy and cell death of the neurons.
- the number of amyloid plaques correlates fairly well with the deterioration of cognitive functions, the neuron loss and the decrease in neurotransmitters (Tanzi et al. 1989) .
- Senile or neuritic plaques consist of an amyloid core, which is surrounded by a periphery comprised of dystrophic neurites and extracellular material.
- the plaques may be dense, so-called classic plaques or diffuse concentrations formed of loosely interconnected material. Diffuse plaques have in fact been assumed to be pre-stages of denser formations, which may form during several years without first causing neurologic symptons (Joachim et al. 1989, Tanzi 1989) .
- amyloid in the senile plaques forms of 6-10 nm stranded ⁇ -amyloid protein, whose identical subunits are arranged antiparallelly into a beta-structure.
- This hydrofobic protein of ca. 4.2-4.5 kDa is synthesized most likely in neurons as part of a longer ⁇ -amyloid precursor protein.
- the gene coding for the precursor protein is localized in the chromosome 21 (Goldgaber et al. 1978, Tanzi 1987) .
- the ⁇ -amyloid precursor is a receptor-like, transmembranal glycosylated protein, in which two thirds are located in the extracellular state (Kang et al. 1987) .
- the ⁇ -amyloid dipeptide is in turn located partly in the transmembranal area so that its proteolytic release from the precursor occurs either before the precursor*s loosening onto or after loosening from cellular membrane (Tanzi 1989) .
- ⁇ -amyloid gene codes for at least three transcripts acting as models for polypeptides with 695, 751 and 770 amino acids.
- the two longer polypep- tides contain an extra sequence with 56 the amino acid, which is 50% homogenous with the enzymes belonging to the so-called Kuniz's serine protease inhibitor family.
- protease inhibitor sequence in the aggregation of the ⁇ -amyloid Two contradictory hypotheses corcerning the possible share of the protease inhibitor sequence in the aggregation of the ⁇ -amyloid have been presented: 1) it may prevent the cumulation of amyloid by inhibiting proteases which release ⁇ -peptide from the precursor, or 2 ) the protease inhibitor may advance the cumulation of amyloid by preventing specific proteinases from purifying the tissue from ⁇ -amyloid.
- the function of the protease inhibitor sequence of the ⁇ -amyloid precursor protein and also its release from the precursor into an active enzyme are thus not known for certain.
- the invention is based on the surprising discovery that oligonucleotides bind to the ⁇ -amyloid protein or its precursor.
- the ⁇ -amyloid protein or its precursor thus binds DNA.
- the binding occurs especially in the ⁇ -amyloid protein or its precursor present in a peripheral tissue (e.g. skin, mucous membrane) .
- the phenomenon may be utilized especially in diagnostic tests (e.g. Alzheimer's disease, Down's syndrome, dementias, old persons).
- the object of our examination was the expression of ⁇ - a yloid on the frontal cortex and hippocampus of Alzheimer patients.
- the RNA in situ hybridization and as a specific tester was a cocktail formed by three short oligonucleotides corresponding to different areas of the ⁇ -amyloid sequence.
- the oligonuc ⁇ leotides were labelled at the 3'-end with biotin.
- antisense-RNA-oligonucleotides were synthesized complementary sense-RNA-oligonucleotides, which were labelled in the same way as the antisense probes.
- the in situ hybridization was performed by using the routine methods of our laboratory (a hybridized biotinylated intron is allowed to bind to a streptavidine-alkaline phosphatase complex, which is in turn detected by means of a substrate reaction) .
- the brain samples of 3 different Alzheimer patients as well as two normal samples were examined. As a result could be observed strong signals in the area of the cortex and hippocampus corresponding both by their location and shape to senile plaques.
- a positive colouring was seen in the walls of blood vessels, as described in connection with the ⁇ -amyloid protein.
- the sense probe we could to our surprise see the same result as when using the antisense probe.
- the in situ hybridization was repeated several times to preclude a possible false positive reaction caused by endogenic biotin or alkaline phosphatase.
- the in situ hybridization was repeated by using a radioactive label or other enzymes for the detection of a biotinylized hybrid (e.g. peroxidase) .
- a biotinylized hybrid e.g. peroxidase
- the results were always the same.
- other oligonucleotides were tested, which deviated from the published sequence of ⁇ -amyloid (e.g. erb cancer gene or 18 and 16 of human papilloma virus (HPV) .
- HPV human papilloma virus
- the location of senile plaques and amyloid was additional ⁇ ly ensured by using conventional stainings: kongo, Bielschowski.
- the samples were additionally stained also immunohistochemically by using as a primary antibody an antibody made against a commercial ⁇ -amyloid protein. These stainings gave considerably weaker signals, but the positive areas were the same.
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pinball Game Machines (AREA)
- Display Devices Of Pinball Game Machines (AREA)
Abstract
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI922392A FI922392L (fi) | 1990-09-27 | 1992-05-25 | Foerfarande foer detektering av b-amyloidprotein genom anvaendning av ospecifik bindning av oligonukleotider. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI904766 | 1990-09-27 | ||
FI904766A FI904766A7 (fi) | 1990-09-27 | 1990-09-27 | Foerfarande foer detektering av protein. |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1992006376A1 true WO1992006376A1 (fr) | 1992-04-16 |
Family
ID=8531126
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FI1991/000300 WO1992006376A1 (fr) | 1990-09-27 | 1991-09-27 | PROCEDE DE DETECTION DE LA PROTEINE β-AMYLOIDE PAR LIAISON NON SPECIFIQUE D'OLIGONUCLEOTIDES |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0503022A1 (fr) |
JP (1) | JPH05502512A (fr) |
CA (1) | CA2069731A1 (fr) |
FI (1) | FI904766A7 (fr) |
WO (1) | WO1992006376A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2256642A (en) * | 1991-06-13 | 1992-12-16 | Ici Plc | Nucleotide sequences for detecting alzheimer's disease |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988003951A1 (fr) * | 1986-11-17 | 1988-06-02 | California Biotechnology, Inc. | Proteine amyloide recombinante relative a la maladie d'alzheimer |
-
1990
- 1990-09-27 FI FI904766A patent/FI904766A7/fi not_active Application Discontinuation
-
1991
- 1991-09-27 JP JP3514942A patent/JPH05502512A/ja active Pending
- 1991-09-27 EP EP91916158A patent/EP0503022A1/fr not_active Withdrawn
- 1991-09-27 WO PCT/FI1991/000300 patent/WO1992006376A1/fr not_active Application Discontinuation
- 1991-09-27 CA CA002069731A patent/CA2069731A1/fr not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988003951A1 (fr) * | 1986-11-17 | 1988-06-02 | California Biotechnology, Inc. | Proteine amyloide recombinante relative a la maladie d'alzheimer |
Non-Patent Citations (2)
Title |
---|
Dialog Information Services, File 155, Medline, Dialog accession No. 07192545, M.R. PALMERT et al., "The beta amyloid protein precursor: mRNAs, membrane-associated forms, and soluble derivatives", Prog Clin Biol Res 1989, 317, p 971-84. * |
Dialog Information Services, File 73, Embase, Dialog accession No. 8232571, S. SYRJANEN et al.: "Short biotinylated oligonucleotides bind non-specifically to senile plaques of Alzheimer's disease", Neurosci, Lett. (Ireland); 1991, 130/1 (89-91). * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2256642A (en) * | 1991-06-13 | 1992-12-16 | Ici Plc | Nucleotide sequences for detecting alzheimer's disease |
GB2256642B (en) * | 1991-06-13 | 1995-12-06 | Ici Plc | Yeast artificial chromosomes comprising nucleotide sequences for the detection of disease alleles |
Also Published As
Publication number | Publication date |
---|---|
FI904766A0 (fi) | 1990-09-27 |
JPH05502512A (ja) | 1993-04-28 |
FI904766A7 (fi) | 1992-03-28 |
EP0503022A1 (fr) | 1992-09-16 |
CA2069731A1 (fr) | 1992-03-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1476758B1 (fr) | Detection et/ou surveillance de maladies liees a la synucleine | |
Mann et al. | An analysis of the morphology of senile plaques in Down's syndrome patients of different ages using immunocytochemical and lectin histochemical techniques | |
US20060134108A1 (en) | Method for retarding or precluding Alzheimer's dementia | |
US5252463A (en) | Clipsin, a chymotrypsin-like protease and method of using same | |
EP2354795A1 (fr) | Procédé et compositions associées à la maladie d'Alzheimer | |
US20090023145A1 (en) | Methods of diagnosing or prognosing Alzheimer's disease | |
JP2005510575A (ja) | アルツハイマー病を予測するig重鎖、igカッパ、igラムダバイオポリマーマーカー | |
WO1992006376A1 (fr) | PROCEDE DE DETECTION DE LA PROTEINE β-AMYLOIDE PAR LIAISON NON SPECIFIQUE D'OLIGONUCLEOTIDES | |
Multhaup et al. | A molecular approach to Alzheimer's disease | |
Navarro et al. | Immunohistochemical presence of apolipoprotein D in senile plaques | |
JP2005510731A (ja) | Ii型糖尿病のスクリーニングのためのフィブリノゲンバイオポリマーマーカーおよびその使用 | |
JP2005523422A (ja) | インスリン耐性を予測するタンパク質バイオポリマーマーカー | |
JP2005510721A (ja) | アルツハイマー病を予測するigラムダバイオポリマーマーカー | |
JP2005510728A (ja) | インスリン耐性を予測するタンパク質バイオポリマーマーカー | |
JP2005510718A (ja) | Ii型糖尿病を予測する補体c3前駆体バイオポリマーマーカー | |
JP2005523420A (ja) | アルツハイマー病を示す補体c3前駆体バイオポリマーマーカー | |
JP2005523419A (ja) | インスリン耐性を示すフィブロネクチンおよびフィブリノゲンバイオポリマーマーカー | |
JP2005525535A (ja) | インスリン耐性を示すマクログロブリンバイオポリマーマーカー | |
Navarro et al. | Apolipoprotein D in Senile Plaques | |
KR20140000977A (ko) | 당뇨망막병증 진단용 마커 및 이의 용도 | |
JP2005510726A (ja) | アルツハイマー病を予測する糖タンパク質およびアポリポタンパク質バイオポリマーマーカー | |
JP2005523425A (ja) | アルツハイマー病を予測するアポリポタンパク質バイオポリマーマーカー | |
JP2005510725A (ja) | アルツハイマー病を予測するフィブロネクチン前駆体バイオポリマーマーカー | |
JP2005510717A (ja) | インスリン耐性を予測するhpバイオポリマーマーカー | |
JP2005510724A (ja) | 年齢にマッチした対照を示すタンパク質バイオポリマーマーカー |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA FI JP US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LU NL SE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1991916158 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 922392 Country of ref document: FI |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2069731 Country of ref document: CA |
|
WWP | Wipo information: published in national office |
Ref document number: 1991916158 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1991916158 Country of ref document: EP |