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1.
Orphanet J Rare Dis ; 19(1): 136, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38532506

ABSTRACT

BACKGROUND: Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is a rare but high invasive subtype of papillary thyroid carcinoma, which mandates an aggressive clinical strategy. Few studies have focused on the sonographic characteristics of DSVPTC and the role of ultrasound in diagnosis and treatment of this variant remains unknown. This study aimed to identify and understand DSVPTC more accurately under ultrasound in correlation with pathology. METHODS: The ultrasound characteristics and histopathologic sections of 10 lesions in 10 DSVPTC patients who underwent thyroid surgery at our center between 2014 and 2020 were reviewed and compared with 184 lesions in 168 classic variant of papillary thyroid carcinoma (cPTC) patients. RESULTS: 6 DSVPTC cases (60%) showed the "snowstorm" pattern on sonogram and 4 cases (40%) presented hypoechoic solid nodules only. Vague borders (100.0% vs. 18.5%, P = 0.019) and abundant microcalcifications (66.7% vs. 10.9%, P = 0.037) were more common in DSVPTC nodules than in cPTC nodules, corresponding to the infiltrating boundaries and numerous psammoma bodies under the microscope respectively. Most of the DSVPTC cases had a heterogeneous background (80%) and suspicious metastatic cervical lymph nodes (80%) on sonograms. All DSVPTC cases had histopathological metastatic cervical lymph nodes. CONCLUSION: The sonographic "snowstorm" pattern indicated DSVPTC with whole-lobe occupation. Hypoechoic solid nodules with vague borders and abundant microcalcifications on sonogram suggested DSVPTC lesion with an ongoing invasion. Regardless of which of the two sonograms was shown, the corresponding DSVPTC lesions were aggressive and required the same attention from the surgeons.


Subject(s)
Calcinosis , Carcinoma, Papillary , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary , Thyroid Neoplasms/diagnosis , Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgery
2.
Quant Imaging Med Surg ; 13(12): 8587-8598, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38106337

ABSTRACT

Background: Ultrasonography of the uterine artery (UtA) in the first and second trimesters of pregnancy can assess uterine-placental blood perfusion and guide early clinical prevention. Establishing normal ranges of the UtA pulsatility index (UtA-PI) at 11-14 weeks of pregnancy is helpful for the early identification of high-risk pregnant women and improving the prognosis. This study aimed to establish a reference range of UtA-PI based on crown-rump length (CRL) for spontaneous and in vitro fertilization (IVF) singleton pregnancy during 11-14 weeks, respectively. Methods: A prospective study was performed at Peking Union Medical College Hospital. Healthy, low-risk women with a singleton pregnancy at 11-14 gestational weeks were consecutively recruited for this study from December 2017 to December 2020. All participants underwent routine prenatal ultrasound examination. The CRL of the fetus and the UtA-PI were measured in both uterine arteries, and average values were calculated. The LMS method was used to fit the percentile (P)5, P10, P25, P50, P75, P90, and P95 curves of the UtA-PI value of spontaneous and IVF singleton pregnancy with CRL changes, respectively. Results: A total of 1,962 pregnant women with normal fetuses were included in this study, including 1,792 pregnancies conceived naturally and 170 IVF fetuses. The UtA-PI reference range in the spontaneous pregnancy group was consistently higher than that in the IVF group during 11-14 weeks, and showed a statistically significant difference in UtA-PI for spontaneous and IVF pregnancies (P<0.001). According to the LMS method, each percentile curve of UtA-PI decreased with the increase of CRL in both the natural pregnancy group and the IVF group. The P95 range of UtA-PI for pregnant women with naturally conceived and IVF pregnancy was 2.74 to 2.11 and 2.50 to 1.94, respectively. The overall change of UtA-PI differentials of the two groups showed a downward trend and decreased slightly with the increase of CRL. Conclusions: This study provided a single-center, large sample of data and constructed a CRL-based reference value of UtA-PI for spontaneous and IVF singleton pregnancy, which provides a reliable basis for early UtA evaluation and early clinical decision-making during 11-14 gestational weeks.

3.
Ultrasonics ; 132: 106987, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36958066

ABSTRACT

The homodyned-K (HK) distribution model is a generalized backscatter envelope statistical model for ultrasound tissue characterization, whose parameters are of physical meaning. To estimate the HK parameters is an inverse problem, and is quite complicated. Previously, we proposed an artificial neural network (ANN) estimator and an improved ANN (iANN) estimator for estimating the HK parameters, which are fast and flexible. However, a drawback of the conventional ANN and iANN estimators consists in that they use Monte Carlo simulations under known values of HK parameters to generate training samples, and thus the ANN and iANN models have to be re-trained when the size of the test sets (or of the envelope samples to be estimated) varies. In addition, conventional ultrasound HK imaging uses a sliding window technique, which is non-vectorized and does not support parallel computation, so HK image resolution is usually sacrificed to ensure a reasonable computation cost. To this end, we proposed a generalized ANN (gANN) estimator in this paper, which took the theoretical derivations of feature vectors for network training, and thus it is independent from the size of the test sets. Further, we proposed a parallelized HK imaging method that is based on the gANN estimator, which used a block-based parallel computation method, rather than the conventional sliding window technique. The gANN-based parallelized HK imaging method allowed a higher image resolution and a faster computation at the same time. Computer simulation experiments showed that the gANN estimator was generally comparable to the conventional ANN estimator in terms of HK parameter estimation performance. Clinical experiments of hepatic steatosis showed that the gANN-based parallelized HK imaging could be used to visually and quantitatively characterize hepatic steatosis, with similar performance to the conventional ANN-based HK imaging that used the sliding window technique, but the gANN-based parallelized HK imaging was over 3 times faster than the conventional ANN-based HK imaging. The parallelized computation method presented in this work can be easily extended to other quantitative ultrasound imaging applications.


Subject(s)
Fatty Liver , Neural Networks, Computer , Humans , Computer Simulation , Ultrasonography/methods , Models, Statistical
4.
Ultrasonics ; 127: 106855, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36206610

ABSTRACT

The segmentation of cardiac chambers and the quantification of clinical functional metrics in dynamic echocardiography are the keys to the clinical diagnosis of heart disease. Identifying the end-diastolic frames (EDFs) and end-systolic frames (ESFs) and manually segmenting the left ventricle in the echocardiographic cardiac cycle before obtaining the left ventricular ejection fraction (LVEF) is a time-consuming and tedious task for clinicians. In this work, we proposed a deep learning-based fully automated echocardiographic analysis method. We proposed a multi-attention efficient feature fusion network (MAEF-Net) to automatically segment the left ventricle. Then, EDFs and ESFs in all cardiac cycles were automatically detected to compute LVEF. The MAEF-Net method used a multi-attention mechanism to guide the network to capture heartbeat features effectively, while suppressing noise, and incorporated deep supervision mechanism and spatial pyramid feature fusion to enhance feature extraction capabilities. The proposed method was validated on the public EchoNet-Dynamic dataset (n = 1226). The Dice similarity coefficient (DSC) of the left ventricular segmentation reached (93.10 ± 2.22)%, and the mean absolute error (MAE) of cardiac phase detection was (2.36 ± 2.23) frames. The MAE for predicting LVEF was 6.29 %. The proposed method was also validated on a private clinical dataset (n = 22). The DSC of the left ventricular segmentation reached (92.81 ± 2.85)%, and the MAE of cardiac phase detection was (2.25 ± 2.27) frames. The MAE for predicting LVEF was 5.91 %, and the Pearson correlation coefficient r reached 0.96. The proposed method may be used as a new method for automatic left ventricular segmentation and quantitative analysis in two-dimensional echocardiography. Our code and trained models will be made available publicly at https://github.com/xiaojinmao-code/MAEF-Net.


Subject(s)
Heart Ventricles , Ventricular Function, Left , Echocardiography , Heart , Heart Ventricles/diagnostic imaging , Image Processing, Computer-Assisted/methods , Stroke Volume
5.
Phys Med Biol ; 66(19)2021 09 24.
Article in English | MEDLINE | ID: mdl-34464947

ABSTRACT

Optical coherence tomography (OCT) is a promising non-invasive imaging technique that owns many biomedical applications. In this paper, a deep neural network is proposed for enhancing the spatial resolution of OCTen faceimages. Different from the previous reports, the proposed can recover high-resolutionen faceimages from low-resolutionen faceimages at arbitrary imaging depth. This kind of imaging depth adaptive resolution enhancement is achieved through an external attention mechanism, which takes advantage of morphological similarity between the arbitrary-depth and full-depthen faceimages. Firstly, the deep feature maps are extracted by a feature extraction network from the arbitrary-depth and full-depthen faceimages. Secondly, the morphological similarity between the deep feature maps is extracted and utilized to emphasize the features strongly correlated to the vessel structures by using the external attention network. Finally, the SR image is recovered from the enhanced feature map through an up-sampling network. The proposed network is tested on a clinical skin OCT data set and an open-access retinal OCT dataset. The results show that the proposed external attention mechanism can suppress invalid features and enhance significant features in our tasks. For all tests, the proposed SR network outperformed the traditional image interpolation method, e.g. bi-cubic method, and the state-of-the-art image super-resolution networks, e.g. enhanced deep super-resolution network, residual channel attention network, and second-order attention network. The proposed method may increase the quantitative clinical assessment of micro-vascular diseases which is limited by OCT imaging device resolution.


Subject(s)
Neural Networks, Computer , Tomography, Optical Coherence , Image Enhancement , Retina/diagnostic imaging
6.
BMC Pregnancy Childbirth ; 21(1): 365, 2021 May 08.
Article in English | MEDLINE | ID: mdl-33964891

ABSTRACT

BACKGROUND: Accurate estimation of fetal weight is important for prenatal care and for detection of fetal growth abnormalities. Prediction of fetal weight entails the indirect measurement of fetal biometry by ultrasound that is then introduced into formulae to calculate the estimated fetal weight. The aim of our study was to evaluate the accuracy of fetal weight estimation of Chinese fetuses in the third trimester using an automated three-dimensional (3D) fractional limb volume model, and to compare this model with the traditional two-dimensional (2D) model. METHODS: Prospective 2D and 3D ultrasonography were performed among women with singleton pregnancies 7 days before delivery to obtain 2D data, including fetal biparietal diameter, abdominal circumference and femur length, as well as 3D data, including the fractional arm volume (AVol) and fractional thigh volume (TVol). The fetal weight was estimated using the 2D model and the 3D fractional limb volume model respectively. Percentage error was defined as (estimated fetal weight - actual birth weight) divided by actual birth weight and multiplied by 100. Systematic errors (accuracy) were evaluated as the mean percentage error (MPE). Random errors (precision) were calculated as ±1 SD of percentage error. The intraclass correlation coefficient (ICC) was used to analyze the inter-observer reliability of the 3D ultrasound measurements of fractional limb volume. RESULTS: Ultrasound examination was performed on 56 fetuses at 39.6 ± 1.4 weeks' gestation. The average birth weight of the newborns was 3393 ± 530 g. The average fetal weight estimated by the 2D model was 3478 ± 467 g, and the MPE was 3.2 ± 8.9. The average fetal weights estimated by AVol and TVol of the 3D model were 3268 ± 467 g and 3250 ± 485 g, respectively, and the MPEs were - 3.3 ± 6.6 and - 3.9 ± 6.1, respectively. For the 3D TVol model, the proportion of fetuses with estimated error ≤ 5% was significantly higher than that of the 2D model (55.4% vs. 33.9%, p < 0.05). For fetuses with a birth weight < 3500 g, the accuracy of the AVol and TVol models were better than the 2D model (- 0.8 vs. 7.0 and - 2.8 vs. 7.0, both p < 0.05). Moreover, for these fetuses, the proportions of estimated error ≤ 5% of the AVol and TVol models were 58.1 and 64.5%, respectively, significantly higher than that of the 2D model (19.4%) (both p < 0.05). The inter-observer reliability of measuring fetal AVol and TVol were high, with the ICCs of 0.921 and 0.963, respectively. CONCLUSION: In this cohort, the automated 3D fractional limb volume model improves the accuracy of weight estimation in most third-trimester fetuses. Prediction accuracy of the 3D model for neonatal BW, particularly < 3500 g was higher than that of the traditional 2D model.


Subject(s)
Fetal Weight , Fetus/diagnostic imaging , Imaging, Three-Dimensional , Thigh/anatomy & histology , Ultrasonography, Prenatal/methods , Adult , Cross-Sectional Studies , Female , Humans , Pregnancy , Pregnancy Trimester, Third , Prospective Studies , Software , Thigh/diagnostic imaging
7.
J Biophotonics ; 14(8): e202100035, 2021 08.
Article in English | MEDLINE | ID: mdl-33991071

ABSTRACT

As an important biomedical imaging method, endoscopic optical coherence tomography (OCT) is necessary to check its performance regularly. The ordinary plane phantoms are only able to evaluate part of image tangent to the probe. In this research, a spatial resolution estimate method of the endoscope OCT system is proposed. The annular phantom, made by uniformly distributing golden scattered microparticles in polydimethylsiloxane (PDMS), can provide dynamic scanning imaging evaluation of endoscopic OCT system, closer to its actual working status. The point spread function analysis method is used to analyze the imaging results of the annular phantom with the endoscopic OCT system. And many scattered particles are statistically analyzed to determine the spatial resolution of the endoscope OCT system. The method is low in cost, simple and convenient. It is valuable for the development of test standards for endoscope OCT systems.


Subject(s)
Endoscopy , Tomography, Optical Coherence , Phantoms, Imaging
8.
Medicine (Baltimore) ; 98(50): e18302, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31852110

ABSTRACT

RATIONALE: The significant ultrasonic characteristics of amniotic band syndrome (ABS) are the malformations of fetal affected parts and the band-like echoes in amniotic cavity. This article first suggests that the fetal hand adhered to umbilical cord with restricted movement provides some values in the diagnosis of ABS in early gestational weeks especially when the fetal malformation is not obvious and amniotic band is thin and fine. PATIENT CONCERNS: Two pregnant women had no discomfort and underwent routine ultrasound examination at 11 to 14 gestational weeks. DIAGNOSIS: Only the fetal hand adhered to umbilical cord with restricted movement was detected during the first ultrasound examination at 11∼14 gestational weeks, and the floating band-like echos were detected in the amniotic cavity with follow-up examinations 2 to 3 weeks later. Both of the 2 fetus were diagnosed as ABS by ultrasound INTERVENTIONS:: The two pregnant women underwent the prenatal counseling and were recommended closely follow-up and further examination. OUTCOMES: Two fetuses died in utero between 17 and 19 weeks. After induction of labor, it was found that the hands and umbilical cord of the fetuses were wrapped by amniotic bands, which was proved pathologically as ABS. LESSONS: The adhesion of the fetal hand and umbilical cord is an important ultrasonic sign suggesting ABS with poor prognosis in early pregnancy. We hope that this study can provide some guidance for the early diagnosis of ABS during 11 to 14 week's ultrasound examination.


Subject(s)
Amniotic Band Syndrome/diagnosis , Early Diagnosis , Fetus/diagnostic imaging , Tissue Adhesions/diagnostic imaging , Umbilical Cord/abnormalities , Adult , Amniotic Band Syndrome/embryology , Fatal Outcome , Female , Gestational Age , Humans , Pregnancy , Tissue Adhesions/embryology , Ultrasonography, Prenatal , Umbilical Cord/diagnostic imaging , Umbilical Cord/embryology
9.
Medicine (Baltimore) ; 98(46): e17873, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31725631

ABSTRACT

RATIONALE: We report a case of fetal lingual cyst that was diagnosed prenatally using 2-dimensional and 3-dimensional images during routine second trimester screening. To the best of our knowledge, this is the first description of a cystic lesion disappearing before birth. PATIENT CONCERNS: A 36-year-old woman at 22 weeks' gestation showed the presence of an oral cystic lesion in routine second trimester ultrasound screening. The lesion measured 18 × 15 × 15 mm. INTERVENTIONS: A follow-up ultrasound examination was performed every 4 to 6 weeks. OUTCOMES: The cyst disappeared in a follow-up ultrasound examination at 35 and 37 weeks of gestation. A male newborn who weighed 3480 g was delivered with no feeding difficulties. The boy was followed to 6 years after birth. The child had normal growth and development, and there was no recurrence of the cyst. LESSONS: Prenatally diagnosed lingual cysts are uncommon findings that can include many different pathologies with a wide spectrum of severity. Lingual cysts usually have a good prognosis.


Subject(s)
Cysts/diagnosis , Prenatal Diagnosis/methods , Tongue Diseases/diagnosis , Adult , Cysts/diagnostic imaging , Female , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Trimester, Second , Tongue Diseases/diagnostic imaging , Ultrasonography, Prenatal
10.
IEEE Trans Med Imaging ; 38(11): 2695-2704, 2019 11.
Article in English | MEDLINE | ID: mdl-30990423

ABSTRACT

In OCT angiography (OCTA), decorrelation computation has been widely used as a local motion index to identify dynamic flow from static tissues, but its dependence on SNR severely degrades the vascular visibility, particularly in low-SNR regions. To mathematically characterize the decorrelation-SNR dependence of OCT signals, we developed a multi-variate time series (MVTS) model. Based on the model, we derived a universal asymptotic linear relation of decorrelation to inverse SNR (iSNR), with the variance in static and noise regions determined by the average kernel size. Accordingly, with the population distribution of static and noise voxels being explicitly calculated in the iSNR and decorrelation (ID) space, a linear classifier is developed by removing static and noise voxels at all SNR, to generate a SNR-adaptive OCTA, termed as ID-OCTA. Then, flow phantom and human skin experiments were performed to validate the proposed ID-OCTA. Both qualitative and quantitative assessments demonstrated that the ID-OCTA offers a superior visibility of blood vessels, particularly in the deep layer. Finally, the implications of this work on both system design and hemodynamic quantification are further discussed.


Subject(s)
Angiography/methods , Image Processing, Computer-Assisted/methods , Tomography, Optical Coherence/methods , Algorithms , Humans , Phantoms, Imaging , Signal-To-Noise Ratio , Skin/blood supply , Skin/diagnostic imaging
11.
Medicine (Baltimore) ; 97(38): e12437, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30235725

ABSTRACT

Fetal adducted thumbs have been described in association with hydrocephalus and other abnormalities, but in cases without other structural malformations the determination of prognosis and recurrence risk is challenging. The aim of our study is to analyze the characteristics, natural history, and postnatal outcome of such cases.A retrospective study was conducted over a period of 4 years in a tertiary referral center. All fetuses diagnosed as adducted thumbs without other structural malformations comprised the study group. Prenatal sonographic features and neonatal outcome are documented.There were 4 cases of fetal adducted thumbs diagnosed during the study period. No cases demonstrated other structural malformations throughout the gestation. A smaller head was noted in 2 cases during the follow-up, and all cases presented with polyhydramnios on the first or ensuing scans. Three cases died after birth due to swallowing or breathing difficulty, and the surviving 1 showed convulsion and mental retardation.Fetal adducted thumb might be an early and specific sonographic marker of impaired neurodevelopment. Close follow-up and genetic investigation should be performed in these cases. Ultrasound examination plays an important role in the prenatal diagnosis and counseling of cases without detailed prenatal genetic analysis.


Subject(s)
Fetus/diagnostic imaging , Genetic Diseases, X-Linked/diagnostic imaging , Hand Deformities/diagnostic imaging , Intellectual Disability/diagnostic imaging , Neurodevelopmental Disorders/diagnostic imaging , Prenatal Diagnosis/instrumentation , Spastic Paraplegia, Hereditary/diagnostic imaging , Thumb/abnormalities , Thumb/diagnostic imaging , Ultrasonography, Prenatal/methods , Brain/diagnostic imaging , Brain/pathology , DNA Copy Number Variations/genetics , Female , Fetus/abnormalities , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/mortality , Gestational Age , Humans , Intellectual Disability/genetics , Intellectual Disability/mortality , Magnetic Resonance Imaging/methods , Male , Polyhydramnios/diagnostic imaging , Pregnancy , Retrospective Studies , Spastic Paraplegia, Hereditary/genetics , Spastic Paraplegia, Hereditary/mortality , Thumb/pathology
12.
Ann Vasc Surg ; 39: 287.e7-287.e13, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27765546

ABSTRACT

Lipoma of the lower leg vein is rare, and the histopathological variant, fibrolipoma, is even rarer. Here, we report an intravascular fibrolipoma located at the junction of the deep femoral vein and the femoral vein in a 50-year-old male patient. Tumor resection and venous reconstruction with a prosthetic graft were performed. Eight months later, the patient was asymptomatic and did not exhibit swelling. To our knowledge, this is the first case report of an intravascular fibrolipoma in the literature. Lower vein venography, computed tomography venography, ultrasonography, and histologic images are presented, along with a description of the procedures employed for tumor resection and venous reconstruction.


Subject(s)
Femoral Vein/pathology , Fibroma/pathology , Lipoma/pathology , Vascular Neoplasms/pathology , Biopsy , Blood Vessel Prosthesis Implantation , Computed Tomography Angiography , Femoral Vein/surgery , Fibroma/surgery , Humans , Lipoma/surgery , Male , Middle Aged , Phlebography/methods , Treatment Outcome , Ultrasonography, Doppler, Color , Vascular Neoplasms/surgery
13.
Biochem J ; 383(Pt. 3): 439-46, 2004 Nov 01.
Article in English | MEDLINE | ID: mdl-15285718

ABSTRACT

IDE (insulin-degrading enzyme) is a widely expressed zinc-metallopeptidase that has been shown to regulate both cerebral amyloid beta-peptide and plasma insulin levels in vivo. Genetic linkage and allelic association have been reported between the IDE gene locus and both late-onset Alzheimer's disease and Type II diabetes mellitus, suggesting that altered IDE function may contribute to some cases of these highly prevalent disorders. Despite the potentially great importance of this peptidase to health and disease, many fundamental aspects of IDE biology remain unresolved. Here we identify a previously undescribed mitochondrial isoform of IDE generated by translation at an in-frame initiation codon 123 nucleotides upstream of the canonical translation start site, which results in the addition of a 41-amino-acid N-terminal mitochondrial targeting sequence. Fusion of this sequence to the N-terminus of green fluorescent protein directed this normally cytosolic protein to mitochondria, and full-length IDE constructs containing this sequence were also directed to mitochondria, as revealed by immuno-electron microscopy. Endogenous IDE protein was detected in purified mitochondria, where it was protected from digestion by trypsin and migrated at a size consistent with the predicted removal of the N-terminal targeting sequence upon transport into the mitochondrion. Functionally, we provide evidence that IDE can degrade cleaved mitochondrial targeting sequences. Our results identify new mechanisms regulating the subcellular localization of IDE and suggest previously unrecognized roles for IDE within mitochondria.


Subject(s)
Codon, Initiator/genetics , Insulysin/genetics , Amino Acid Sequence/genetics , Animals , CHO Cells/chemistry , Cell Line , Conserved Sequence/genetics , Cricetinae , Cricetulus , Humans , Immunohistochemistry/methods , Insulysin/physiology , Insulysin/ultrastructure , Isoenzymes/genetics , Isoenzymes/physiology , Isoenzymes/ultrastructure , Kidney/chemistry , Kidney/cytology , Kidney/embryology , Methionine/genetics , Mice , Microscopy, Electron/methods , Mitochondria/enzymology , Mitochondria/ultrastructure , Mitochondrial Proteins/genetics , Mitochondrial Proteins/physiology , Mitochondrial Proteins/ultrastructure , Molecular Sequence Data , Rats , Sequence Alignment/methods , Sequence Homology, Nucleic Acid , Submitochondrial Particles/ultrastructure
14.
Neuron ; 40(6): 1087-93, 2003 Dec 18.
Article in English | MEDLINE | ID: mdl-14687544

ABSTRACT

Converging evidence suggests that the accumulation of cerebral amyloid beta-protein (Abeta) in Alzheimer's disease (AD) reflects an imbalance between the production and degradation of this self-aggregating peptide. Upregulation of proteases that degrade Abeta thus represents a novel therapeutic approach to lowering steady-state Abeta levels, but the consequences of sustained upregulation in vivo have not been studied. Here we show that transgenic overexpression of insulin-degrading enzyme (IDE) or neprilysin (NEP) in neurons significantly reduces brain Abeta levels, retards or completely prevents amyloid plaque formation and its associated cytopathology, and rescues the premature lethality present in amyloid precursor protein (APP) transgenic mice. Our findings demonstrate that chronic upregulation of Abeta-degrading proteases represents an efficacious therapeutic approach to combating Alzheimer-type pathology in vivo.


Subject(s)
Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Peptide Hydrolases/biosynthesis , Plaque, Amyloid/metabolism , Amyloid beta-Peptides/genetics , Amyloid beta-Protein Precursor/genetics , Animals , Female , Humans , Insulysin/biosynthesis , Insulysin/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neprilysin/biosynthesis , Neprilysin/genetics , Peptide Hydrolases/genetics , Plaque, Amyloid/genetics , Plaque, Amyloid/pathology , Pregnancy , Survival Rate , Up-Regulation/physiology
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