The Value of NOTCH2NLC Gene Detection and Skin Biopsy

The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease

 

The clinical manifestations of neuronal intranuclear inclusion disease (NIID) are heterogeneous, and the premortem diagnosis is mainly based on skin biopsy findings. Abnormal GGC repeat expansions in NOTCH2NLC was recently identified in familial and sporadic NIID. The comparison of diagnostic value between abnormal GGC repeat expansions of NOTCH2NLC and skin biopsy has not been conducted yet.
In this study, skin biopsy was performed in 10 suspected adult NIID patients with clinical and imaging manifestations, and GGC repeat size in NOTCH2NLC was also screened by repeat primed-PCR and GC-rich PCR. We found that five cases had ubiquitin-immunolabelling intranuclear inclusion bodies by skin biopsy, and all of them were identified with abnormal GGC repeat expansions in NOTCH2NLC, among whom four patients showed typical linear hyperintensity at corticomedullary junction on DWI.
Five (5/10) NIID patients were diagnosed by combination of NOTCH2NLC gene detection, skin biopsy or combination of NOTCH2NLC, and typical MRI findings. The diagnostic performance of NOTCH2NLC gene detection was highly consistent with that of skin biopsy (Kappa = 1). The unexplained headache was firstly reported as a new early phenotype of NIID. These findings indicate that NOTCH2NLC gene detection is needed to be a supplement in the diagnose flow of NIID and also may be used as an alternative method to skin biopsy especially in Asian population.
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EpCAM Antigen

E64B00107 0.1mg
EUR 343

Human epithelial specific antigen(ESA)ELISA Kit

GA-E1696HM-48T 48T
EUR 289

Human epithelial specific antigen(ESA)ELISA Kit

GA-E1696HM-96T 96T
EUR 466

Human epithelial specific antigen,ESA ELISA Kit

201-12-1680 96 tests
EUR 440
Description: A quantitative ELISA kit for measuring Human in samples from biological fluids.

Anti-Ep-CAM/Epithelial Specific Antigen antibody

STJ16100363 1 mL
EUR 868

Human epithelial specific antigen(ESA)ELISA Kit

QY-E01682 96T
EUR 361

Human epithelial specific antigen,ESA ELISA Kit

CN-04610H1 96T
EUR 442

Human epithelial specific antigen,ESA ELISA Kit

CN-04610H2 48T
EUR 293

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx129957
  • EUR 467.00
  • EUR 133.00
  • EUR 1344.00
  • EUR 634.00
  • EUR 356.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx125330
  • EUR 495.00
  • EUR 704.00
  • EUR 356.00
  • 100 ul
  • 200 ul
  • 50 ul

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx112318
  • EUR 732.00
  • EUR 398.00
  • 150 ul
  • 50 ul

Epithelial Cell Adhesion Molecule (EpCAM) Antibody

20-abx123431
  • EUR 495.00
  • EUR 704.00
  • EUR 356.00
  • 100 ul
  • 200 ul
  • 50 ul

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx104775
  • EUR 439.00
  • EUR 133.00
  • EUR 1233.00
  • EUR 592.00
  • EUR 328.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Epithelial Cell Adhesion Molecule (EpCAM) Antibody

abx037446-100ug 100 ug
EUR 391

Epithelial Cell Adhesion Molecule (EpCAM) Antibody

abx037447-100ug 100 ug
EUR 391

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

abx011925-100ul 100 ul
EUR 411

Epithelial Cell Adhesion Molecule (EpCAM) Antibody

abx030033-400ul 400 ul
EUR 523

Epithelial Cell Adhesion Molecule (EpCAM) Antibody

abx030033-80l 80 µl
EUR 286

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

abx430513-200ul 200 ul
EUR 384

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx172278
  • EUR 815.00
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  • 1 mg
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Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx270202
  • EUR 467.00
  • EUR 537.00
  • EUR 272.00
  • EUR 815.00
  • EUR 356.00
  • 100 tests
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Epithelial Cell Adhesion Molecule (EPCAM) Antibody

abx224065-100ug 100 ug
EUR 411

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx338680
  • EUR 411.00
  • EUR 1845.00
  • EUR 599.00
  • EUR 182.00
  • EUR 300.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

abx159488-100ul 100 ul
EUR 467

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx242428
  • EUR 411.00
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  • 100 ul
  • 50 ul

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx242433
  • EUR 411.00
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  • 100 ul
  • 50 ul

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx214622
  • EUR 411.00
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  • 100 ul
  • 50 ul

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

abx232799-100ug 100 ug
EUR 509

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx176308
  • EUR 411.00
  • EUR 133.00
  • EUR 1149.00
  • EUR 565.00
  • EUR 314.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

abx331190-100ul 100 ul
EUR 425

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx327226
  • EUR 314.00
  • EUR 244.00
  • 100 ug
  • 50 ug

Epithelial Cell Adhesion Molecule (EPCAM) Antibody

20-abx324346
  • EUR 314.00
  • EUR 244.00
  • 100 ug
  • 50 ug

Human Epithelial cell adhesion molecule (EPCAM)

1-CSB-EP007717HU
  • EUR 380.00
  • EUR 214.00
  • EUR 1309.00
  • EUR 560.00
  • EUR 873.00
  • EUR 262.00
  • 100ug
  • 10ug
  • 1MG
  • 200ug
  • 500ug
  • 50ug
Description: Recombinant Human Epithelial cell adhesion molecule(EPCAM),partial expressed in E.coli

Recombinant Epithelial Cell Adhesion Molecule (EPCAM)

4-RPB283Ga01
  • EUR 530.08
  • EUR 245.00
  • EUR 1712.80
  • EUR 637.60
  • EUR 1175.20
  • EUR 418.00
  • EUR 4132.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Chicken Epithelial Cell Adhesion Molecule expressed in: E.coli

Recombinant Epithelial Cell Adhesion Molecule (EPCAM)

4-RPB283Hu01
  • EUR 440.48
  • EUR 221.00
  • EUR 1376.80
  • EUR 525.60
  • EUR 951.20
  • EUR 358.00
  • EUR 3292.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Human Epithelial Cell Adhesion Molecule expressed in: E.coli

Recombinant Epithelial Cell Adhesion Molecule (EPCAM)

4-RPB283Po01
  • EUR 548.00
  • EUR 250.00
  • EUR 1780.00
  • EUR 660.00
  • EUR 1220.00
  • EUR 430.00
  • EUR 4300.00
  • 100 ug
  • 10ug
  • 1 mg
  • 200 ug
  • 500 ug
  • 50ug
  • 5 mg
Description: Recombinant Pig Epithelial Cell Adhesion Molecule expressed in: E.coli

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC942041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF594 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC942041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF594 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNCA2041-250 250uL
EUR 394
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), APC conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC812041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF680R conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC812041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF680R conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNCAP2041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), Alkaline Phosphatase conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNCAP2041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), Alkaline Phosphatase conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC472041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF647 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC472041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF647 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC432041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF543 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC432041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF543 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC882041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF488A conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC882041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF488A conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNCH2041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), Horseradish Peroxidase conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNCH2041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), Horseradish Peroxidase conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNCP2041-250 250uL
EUR 394
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), PerCP conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC042041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF405S conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC042041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF405S conjugate, Concentration: 0.1mg/mL

Chicken Epithelial Cell Adhesion Molecule (EPCAM) Protein

20-abx168032
  • EUR 732.00
  • EUR 286.00
  • EUR 2305.00
  • EUR 885.00
  • EUR 523.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Epithelial Cell Adhesion Molecule (EPCAM) Antibody (FITC)

20-abx270500
  • EUR 523.00
  • EUR 606.00
  • EUR 300.00
  • EUR 940.00
  • EUR 384.00
  • 100 tests
  • 200 tests
  • 25 tests
  • 500 tests
  • 50 tests

Epithelial Cell Adhesion Molecule (EPCAM) Antibody (APC)

20-abx270732
  • EUR 704.00
  • EUR 829.00
  • EUR 370.00
  • EUR 1330.00
  • EUR 495.00
  • 100 tests
  • 200 tests
  • 25 tests
  • 500 tests
  • 50 tests

Epithelial Cell Adhesion Molecule (EPCAM) Antibody (PE)

20-abx270964
  • EUR 606.00
  • EUR 718.00
  • EUR 328.00
  • EUR 1135.00
  • EUR 439.00
  • 100 tests
  • 200 tests
  • 25 tests
  • 500 tests
  • 50 tests

Pig Epithelial Cell Adhesion Molecule (EPCAM) Protein

20-abx167541
  • EUR 759.00
  • EUR 300.00
  • EUR 2388.00
  • EUR 913.00
  • EUR 537.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Epithelial Cell Adhesion Molecule (EPCAM) Antibody (FITC)

abx140496-100tests 100 tests
EUR 425

Epithelial Cell Adhesion Molecule (EPCAM) Antibody (PE)

abx140492-100tests 100 tests
EUR 481

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNCR2041-250 250uL
EUR 394
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), RPE conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNUB2041-100 100uL
EUR 264
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), Concentration: 0.2mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNUB2041-50 50uL
EUR 405
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), 1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNUB2041-500 500uL
EUR 513
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), Concentration: 0.2mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC612041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF660R conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC612041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF660R conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC682041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF568 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC682041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF568 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC702041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF770 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC702041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF770 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC052041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF405M conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC052041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF405M conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC552041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF555 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC552041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF555 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC402041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF640R conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC402041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF640R conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC802041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF680 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNC802041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), CF680 conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNCB2041-100 100uL
EUR 233
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), Biotin conjugate, Concentration: 0.1mg/mL

EpCAM / CD326 (Epithelial Marker) (EGP40/2041R) Antibody

BNCB2041-500 500uL
EUR 545
Description: Primary antibody against EpCAM / CD326 (Epithelial Marker) (EGP40/2041R), Biotin conjugate, Concentration: 0.1mg/mL

Epithelial Cell Adhesion Molecule (EPCAM) Antibody (HRP)

20-abx335604
  • EUR 411.00
  • EUR 1845.00
  • EUR 599.00
  • EUR 182.00
  • EUR 300.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Epithelial Cell Adhesion Molecule (EPCAM) Antibody (FITC)

20-abx335605
  • EUR 411.00
  • EUR 1845.00
  • EUR 599.00
  • EUR 182.00
  • EUR 300.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Epithelial Cell Adhesion Molecule (EPCAM) Antibody (Biotin)

20-abx335606
  • EUR 411.00
  • EUR 1845.00
  • EUR 599.00
  • EUR 182.00
  • EUR 300.00
  • 100 ug
  • 1 mg
  • 200 ug
  • 20 ug
  • 50 ug

Human Epithelial Cell Adhesion Molecule (EPCAM) Protein

20-abx652155
  • EUR 620.00
  • EUR 272.00
  • EUR 1859.00
  • EUR 732.00
  • EUR 453.00
  • 100 ug
  • 10 ug
  • 1 mg
  • 200 ug
  • 50 ug

Cow Epithelial Cell Adhesion Molecule (EPCAM) ELISA Kit

abx516210-96tests 96 tests
EUR 911

Human Epithelial Cell Adhesion Molecule (EPCAM) ELISA Kit

abx516212-96tests 96 tests
EUR 668

Mouse Epithelial Cell Adhesion Molecule (EPCAM) ELISA Kit

abx516213-96tests 96 tests
EUR 707

Rat Epithelial Cell Adhesion Molecule (EPCAM) ELISA Kit

abx516215-96tests 96 tests
EUR 668

Human Epithelial Cell Adhesion Molecule, EPCAM ELISA Kit

DEIA244 5 plates
EUR 1344
Description: The human EPCAM ELISA kit is for the quantitative determination of human EPCAM.

Human EPCAM/ Epithelial cell adhesion molecule ELISA Kit

E0800Hu 1 Kit
EUR 571

Human Epithelial Cell Adhesion Molecule (EPCAM) CLIA Kit

20-abx492586
  • EUR 7973.00
  • EUR 4246.00
  • EUR 981.00
  • 10 × 96 tests
  • 5 × 96 tests
  • 96 tests

digIS: towards detecting distant and putative novel insertion sequence elements in prokaryotic genomes

Background: The insertion sequence elements (IS elements) represent the smallest and the most abundant mobile elements in prokaryotic genomes. It has been shown that they play a significant role in genome organization and evolution. To better understand their function in the host genome, it is desirable to have an effective detection and annotation tool.

This need becomes even more crucial when considering rapid-growing genomic and metagenomic data. The existing tools for IS elements detection and annotation are usually based on comparing sequence similarity with a database of known IS families. Thus, they have limited ability to discover distant and putative novel IS elements.

Results: In this paper, we present digIS, a software tool based on profile hidden Markov models assembled from catalytic domains of transposases. It shows a very good performance in detecting known IS elements when tested on datasets with manually curated annotation. The main contribution of digIS is in its ability to detect distant and putative novel IS elements while maintaining a moderate level of false positives. In this category it outperforms existing tools, especially when tested on large datasets of archaeal and bacterial genomes.

Conclusion: We provide digIS, a software tool using a novel approach based on manually curated profile hidden Markov models, which is able to detect distant and putative novel IS elements. Although digIS can find known IS elements as well, we expect it to be used primarily by scientists interested in finding novel IS elements.

Gene Expression Changes in a Model Neuron Cell Line Exposed to Autoantibodies from Patients with Traumatic Brain Injury and/or Type 2 Diabetes

Traumatic brain injury and adult type 2 diabetes mellitus are each associated with the late occurrence of accelerated cognitive decline and Parkinson’s disease through unknown mechanisms. Previously, we reported increased circulating agonist autoantibodies targeting the 5-hydroxytryptamine 2A receptor in plasma from subsets of Parkinson’s disease, dementia, and diabetic patients suffering with microvascular complications.
Here, we use a model neuron, mouse neuroblastoma (N2A) cell line, to test messenger RNA expression changes following brief exposure to traumatic brain injury and/or type 2 diabetes mellitus plasma harboring agonist 5-hydroxytryptamine 2A receptor autoantibodies.
We now report involvement of the mitochondrial dysfunction pathway and Parkinson’s disease pathways in autoantibody-induced gene expression changes occurring in neuroblastoma cells. Functional gene categories upregulated significantly included cell death, cytoskeleton-microtubule function, actin polymerization or depolymerization, regulation of cell oxidative stress, mitochondrial function, immune function, protein metabolism, and vesicle function.
Gene categories significantly downregulated included microtubule function, cell adhesion, neurotransmitter release, dopamine metabolism synaptic plasticity, maintenance of neuronal differentiation, mitochondrial function, and cell signaling.
Taken together, these results suggest that agonist 5-hydroxytryptamine receptor autoantibodies (which increase in Parkinson’s disease and other forms of neurodegeneration) mediate a coordinating program of gene expression changes in a model neuron which predispose to neuro-apoptosis and are linked to human neurodegenerative diseases pathways.

Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers

Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with a complex genetic etiology. Besides the apolipoprotein E ε4 (APOE ε4) allele, a few dozen other genetic loci associated with AD have been identified through genome-wide association studies (GWAS) conducted mainly in individuals of European ancestry.
Recently, several GWAS performed in other ethnic groups have shown the importance of replicating studies that identify previously established risk loci and searching for novel risk loci. APOE-stratified GWAS have yielded novel AD risk loci that might be masked by, or be dependent on, APOE alleles.
We performed whole-genome sequencing (WGS) on DNA from blood samples of 331 AD patients and 169 elderly controls of Korean ethnicity who were APOE ε4 carriers. Based on WGS data, we designed a customized AD chip (cAD chip) for further analysis on an independent set of 543 AD patients and 894 elderly controls of the same ethnicity, regardless of their APOE ε4 allele status.
Combined analysis of WGS and cAD chip data revealed that SNPs rs1890078 (P = 6.64E-07) and rs12594991 (P = 2.03E-07) in SORCS1 and CHD2 genes, respectively, are novel genetic variants among APOE ε4 carriers in the Korean population.
In addition, nine possible novel variants that were rare in individuals of European ancestry but common in East Asia were identified. This study demonstrates that APOE-stratified analysis is important for understanding the genetic background of AD in different populations.

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