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1. (WO2019009985) SPECIALIZED EXCITATORY SYNAPTIC PROTEIN BIOMARKERS OF PLASMA NEURONAL EXOSOMES FOR PREDICTION AND STAGING OF ALZHEIMER'S DISEASE
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Pub. No.: WO/2019/009985 International Application No.: PCT/US2018/036909
Publication Date: 10.01.2019 International Filing Date: 11.06.2018
IPC:
G01N 33/68 (2006.01) ,A61P 25/28 (2006.01) ,C12Q 1/68 (2018.01) ,C12Q 1/6813 (2018.01) ,G01N 33/48 (2006.01) ,G01N 33/50 (2006.01)
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
50
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
68
involving proteins, peptides or amino acids
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
25
Drugs for disorders of the nervous system
28
for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
Q
MEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICRO-ORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
1
Measuring or testing processes involving enzymes or micro-organisms; Compositions therefor; Processes of preparing such compositions
68
involving nucleic acids
[IPC code unknown for C12Q 1/6813]
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
50
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
Applicants:
GOETZL, Edward, J. [US/US]; US
Inventors:
GOETZL, Edward, J.; US
Agent:
BREINER, Mary, J.; US
BREINER, Theodore, A.; US
Priority Data:
62/528,56705.07.2017US
Title (EN) SPECIALIZED EXCITATORY SYNAPTIC PROTEIN BIOMARKERS OF PLASMA NEURONAL EXOSOMES FOR PREDICTION AND STAGING OF ALZHEIMER'S DISEASE
(FR) BIOMARQUEURS DE PROTÉINES SYNAPTIQUES EXCITATOIRES SPÉCIALISÉS D'EXOSOMES NEURONAUX PLASMATIQUES DESTINÉS À LA PRÉDICTION ET À LA STADIFICATION DE LA MALADIE D'ALZHEIMER
Abstract:
(EN) Combining presynaptic proteins, neuronal pentraxin 2 (NPTX2) and neurexin 2α (NRXN2a), with respective postsynaptic functional partners GluA4-containing glutamate receptor (AMPA4) and neuroligin 1 (NLGN1), and enhancing excitatory synaptic activities in areas of the hippocampus and cerebral cortex. As early damage of such excitatory circuits in Alzheimer' s disease (AD) correlates with cognitive losses, plasma neuron- derived exosome (NDE) levels of these two pairs of synaptic proteins are quantified and serve as biomarkers. NDE contents of all four proteins decrease significantly in AD dementia and diminished levels of AMPA4 and NLGN1 correlate with the extent of cognitive losses. Prior to the onset of dementia, NDE levels of all but NPTX2 are significantly lower than those of matched control subjects and levels of all decline significantly with the development of dementia. Reductions in NDE levels of these excitatory synaptic proteins are indicators of cognitive losses and reflect progression of severity of AD.
(FR) L'invention concerne la combinaison de protéines présynaptiques, pentraxine 2 neuronale (NPTX2) et neuréxine 2a (NRXN2a), à des partenaires fonctionnels postsynaptiques respectifs récepteur du glutamate contenant du GluA4 (AMPA4) et neuroligine 1 (NLGN1), et l'amélioration d'activités synaptiques excitatrices dans des zones de l'hippocampe et du cortex cérébral. À mesure que des dommages précoces desdits circuits excitateurs dans la maladie d'Alzheimer (AD) sont en corrélation avec des pertes cognitives, des niveaux d'exosomes dérivés de neurones (NDE) plasmatiques des deux paires précitées de protéines synaptiques sont quantifiés et servent de biomarqueurs. Les teneurs en NDE des quatre protéines diminuent de manière significative dans la démence AD et les niveaux diminués de AMPA4 et NLGN1 sont en corrélation avec l'étendue des pertes cognitives. Avant l'apparition de la démence, tous les niveaux de NDE sauf ceux des NPTX2 sont significativement inférieurs à ceux des sujets témoins appariés et les niveaux de toutes déclinent de manière significative avec le développement de la démence. Des réductions de niveaux de NDE desdites protéines synaptiques excitatrices constituent des indicateurs de pertes cognitives et reflètent la progression de la gravité de l'AD.
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Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)