High throughput automated characterization of enamel microstructure using synchrotron tomography and optical flow imaging.

The remarkable damage-tolerance of enamel has been attributed to its hierarchical microstructure and the organized bands of decussated rods. A thorough characterization of the microscale rod evolution within the enamel is needed to elucidate this complex structure. While prior efforts in this area have made use of single particle tracking to track a single rod evolution to various degrees of success, such a process can be both computationally and labor intensive, limited to the evolution path of a single rod, and is therefore prone to error from potentially tracking outliers. Particle image velocimetry (PIV) is a well-established algorithm to derive field information from image sequences for processes that are time-dependent, such as fluid flows and structural deformation. In this work, we demonstrate the use of PIV in extracting the full-field microstructural distribution of rods within the enamel. Enamel samples from a wild African lion were analyzed using high-energy synchrotron X-ray micro-tomography. Results from the PIV analysis provide sufficient full-field information to reconstruct the growth of individual rods that can potentially enable rapid analysis of complex microstructures from high resolution synchrotron datasets. Such information can serve as a template for designing damage-tolerant bioinspired structures for advanced manufacturing. STATEMENT OF SIGNIFICANCE: Thorough characterization and analysis of biological microstructures (viz. dental enamel) allows us to understand the basis of their excellent mechanical properties. Prior efforts have successfully replicated these microstructures via single particle tracking, but the process is computationally and labor intensive. In this work, optical flow imaging algorithms were used to extract full-field microstructural distribution of enamel rods from synchrotron X-ray computed tomography datasets, and a field method was used to reconstruct the growth of individual rods. Such high throughput information allows for the rapid production/prototyping and advanced manufacturing of damage-tolerant bioinspired structures for specific engineering applications. Furthermore, the algorithms used herein are freely available and open source to broaden the availability of the proposed workflow to the general scientific community.

Characterizing the microstructures of mammalian enamel by synchrotron phase contrast microCT.

The enamel of mammalian teeth is a highly mineralized tissue that must endure a lifetime of cyclic contact and is inspiring the development of next-generation engineering materials. Attempts to implement enamel-inspired structures in synthetic materials have had limited success, largely due to the absence of a detailed understanding of its microstructure. The present work used synchrotron phase-contrast microCT imaging to evaluate the three-dimensional microstructure of enamel from four mammals including Lion, Gray Wolf, Snow Leopard, and Black Bear. Quantitative results of image analysis revealed that the decussation pattern of enamel consists of discrete diazone (D) and parazone (P) bands of rods organized with stacking arrangement of D+/P/D-/P in all mammals evaluated; the D+ and D- refer to distinct diazone bands with juxtaposed rod orientations from the reference plane. Furthermore, the rod orientations in the bands can be described in terms of two principal angles, defined here as the pitch and yaw. While the pitch angle increases from the outer enamel to a maximum (up to ≈ 40°) near the dentin enamel junction, minimal spatial variations are observed in yaw across the enamel thickness. There are clear differences in the decussation parameters of enamel across species that are interpreted here with respect to the structural demands placed on their teeth. The rod pitch and band width of enamel are identified as important design parameters and appear to be correlated with the bite force quotient of the four mammals evaluated. STATEMENT OF SIGNIFICANCE: The multi-functionality of tooth enamel requires both hardness and resistance to fracture, properties that are generally mutually exclusive. Ubiquitous to all mammalian teeth, the enamel is expected to have undergone adaptations in microstructure to accommodate the differences in diet, body size and bite force across animals. For the first time, we compare the complex three-dimensional microstructure of enamel from teeth of multiple mammalian species using synchrotron micro-computed tomography. The findings provide new understanding of the "design" of mammalian enamel microstructures, as well as how specific parameters associated with the decussation of rods appear to be engineered to modulate its fracture resistance.

Mammalian enamel: A universal tissue and diverse source of inspiration.

The natural armors and weapons of the animal kingdom are serving as inspiration in the development of next-generation engineering materials. In this pursuit, seldom considered are the variations in properties across taxa that have evolved to meet their unique functional demands. Here, teeth from six different mammalian species were acquired and categorized according to their bite force quotient (BFQ), which accounts for the allometric scaling between bite force and body size. Selected chemical, microstructural, and mechanical properties of the enamel were quantified across the enamel thickness using spectroscopy and indentation techniques. Results showed that the chemical composition of enamel was significantly (P <  0.05) different between the Low and High BFQ groups, whereas the apatite crystallinity was not. The enamel of all animals exhibited a spatial gradient in mechanical properties that was consistent when evaluated using a normalized framework. Although the elastic modulus, hardness and indentation brittleness were significantly lower in the High BFQ group, the fracture resistance of enamel was significantly higher in this group, potentially reflective of bite force requirements related to diet and predation. Enamel rod decussation was present in all teeth, but there were differences in specific microstructural features. Overall, these results highlight that the diversity of tooth enamel across species should be considered in the pursuit of nature-inspired structural materials. STATEMENT OF SIGNIFICANCE: Natural weapons are serving as inspiration in the development of next-generation engineering materials. Tooth enamel is a viable candidate, but variations in the structure and properties of enamel across taxa have not been explored. Here, teeth from six different mammalian species were categorized according to their bite force quotient (BFQ), and the enamel was compared in terms of selected chemical, microstructural, and mechanical properties. We show that specific aspects of the chemical composition and properties of the Low and High BFQ groups are unique, which appears reflective of bite forces associated with diet and predation. Overall, the results highlight that the diversity of tooth enamel across species should be considered in the pursuit of nature-inspired structural materials.

Fluorescence Emission Triggered by Radioactive ß decay in Optimized Hyperbolic Cavities.

Luminescence arising from ß -decay of radiotracers has garnered much interest recently as a viable in-vivo imaging technique. The emitted Cerenkov radiation can be directly detected by high sensitivity cameras or used to excite highly efficient fluorescent dyes. Here, we investigate the enhancement of visible and infrared emission driven by ß -decay of radioisotopes in the presence of a hyperbolic nanocavity. By means of a transfer matrix approach, we obtain quasi-analytic expressions for the fluorescence enhancement factor at the dielectric core of the metalodielectric cavity, reporting a hundred-fold amplification in periodic structures. A particle swarm optimization of the layered shell geometry reveals that up to a ten-thousand-fold enhancement is possible thanks to the hybridization and spectral overlapping of whispering-gallery and localized-plasmon modes. Our findings may find application in nuclear-optical medical imaging, as they provide a strategy for the exploitation of highly energetic gamma rays, Cerenkov luminescence, and visible and near-infrared fluorescence through the same nanotracer.

Mapping in-vivo optic nerve head strains caused by intraocular and intracranial pressures.

Although it is well documented that abnormal levels of either intraocular (IOP) or intracranial pressure (ICP) can lead to potentially blinding conditions, such as glaucoma and papilledema, little is known about how the pressures actually affect the eye. Even less is known about potential interplay between their effects, namely how the level of one pressure might alter the effects of the other. Our goal was to measure in-vivo the pressure-induced stretch and compression of the lamina cribrosa due to acute changes of IOP and ICP. The lamina cribrosa is a structure within the optic nerve head, in the back of the eye. It is important because it is in the lamina cribrosa that the pressure-induced deformations are believed to initiate damage to neural tissues leading to blindness. An eye of a rhesus macaque monkey was imaged in-vivo with optical coherence tomography while IOP and ICP were controlled through cannulas in the anterior chamber and lateral ventricle, respectively. The image volumes were analyzed with a newly developed digital image correlation technique. The effects of both pressures were highly localized, nonlinear and non-monotonic, with strong interactions. Pressure variations from the baseline normal levels caused substantial stretch and compression of the neural tissues in the posterior pole, sometimes exceeding 20%. Chronic exposure to such high levels of biomechanical insult would likely lead to neural tissue damage and loss of vision. Our results demonstrate the power of digital image correlation technique based on non-invasive imaging technologies to help understand how pressures induce biomechanical insults and lead to vision problems.

Risk Factors for De Novo Malignancy Following Lung Transplantation.

Risk factors for non-skin cancer de novo malignancy (DNM) after lung transplantation have yet to be identified. We queried the United Network for Organ Sharing database for all adult lung transplant patients between 1989 and 2012. Standardized incidence ratios (SIRs) were computed by comparing the data to Surveillance, Epidemiology, and End Results Program data after excluding skin squamous/basal cell carcinomas. We identified 18 093 adult lung transplant patients; median follow-up time was 1086 days (interquartile range 436-2070). DNMs occurred in 1306 patients, with incidences of 1.4%, 4.6%, and 7.9% at 1, 3, and 5 years, respectively. The overall cancer incidence was elevated compared with that of the general US population (SIR 3.26, 95% confidence interval [CI]: 2.95-3.60). The most common cancer types were lung cancer (26.2% of all malignancies, SIR 6.49, 95% CI: 5.04-8.45) and lymphoproliferative disease (20.0%, SIR 14.14, 95% CI: 9.45-22.04). Predictors of DNM following lung transplantation were age (hazard ratio [HR] 1.03, 95% CI: 1.02-1.05, p < 0.001), male gender (HR 1.20, 95% CI: 1.02-1.42, p = 0.03), disease etiology (not cystic fibrosis, idiopathic pulmonary fibrosis or interstitial lung disease, HR 0.59, 95% CI 0.37-0.97, p = 0.04) and single-lung transplantation (HR 1.64, 95% CI: 1.34-2.01, p < 0.001). Significant interactions between donor or recipient smoking and single-lung transplantation were noted. On multivariable survival analysis, DNMs were associated with an increased risk of mortality (HR 1.44, 95% CI: 1.10-1.88, p = 0.009).

Simulated Regionalization of Heart and Lung Transplantation in the United States.

We simulated the impact of regionalization of isolated heart and lung transplantation within United Network for Organ Sharing (UNOS) regions. Overall, 12 594 orthotopic heart transplantation (OHT) patients across 135 centers and 12 300 orthotopic lung transplantation (OLT) patients across 67 centers were included in the study. An algorithm was constructed that "closed" the lowest volume center in a region and referred its patients to the highest volume center. In the unadjusted analysis, referred patients were assigned the highest volume center's 1-year mortality rate, and the difference in deaths per region before and after closure was computed. An adjusted analysis was performed using multivariable logistic regression using recipient and donor variables. The primary outcome was the potential number of lives saved at 1 year after transplant. In adjusted OHT analysis, 10 lives were saved (95% confidence interval [CI] 9-11) after one center closure and 240 lives were saved (95% CI 209-272) after up to five center closures per region, with the latter resulting in 1624 total patient referrals (13.2% of OHT patients). For OLT, lives saved ranged from 29 (95% CI 26-32) after one center closure per region to 240 (95% CI 224-256) after up to five regional closures, but the latter resulted in 2999 referrals (24.4% of OLT patients). Increased referral distances would severely limit access to care for rural and resource-limited populations.

What is a typical optic nerve head?

Whereas it is known that elevated intraocular pressure (IOP) increases the risk of glaucoma, it is not known why optic nerve heads (ONHs) vary so much in sensitivity to IOP and how this sensitivity depends on the characteristics of the ONH such as tissue mechanical properties and geometry. It is often assumed that ONHs with uncommon or atypical sensitivity to IOP, high sensitivity in normal tension glaucoma or high robustness in ocular hypertension, also have atypical ONH characteristics. Here we address two specific questions quantitatively: Do atypical ONH characteristics necessarily lead to atypical biomechanical responses to elevated IOP? And, do typical biomechanical responses necessarily come from ONHs with typical characteristics. We generated 100,000 ONH numerical models with randomly selected values for the characteristics, all falling within literature ranges of normal ONHs. The models were solved to predict their biomechanical response to an increase in IOP. We classified ONH characteristics and biomechanical responses into typical or atypical using a percentile-based threshold, and calculated the fraction of ONHs for which the answers to the two questions were true and/or false. We then studied the effects of varying the percentile threshold. We found that when we classified the extreme 5% of individual ONH characteristics or responses as atypical, only 28% of ONHs with an atypical characteristic had an atypical response. Further, almost 29% of typical responses came from ONHs with at least one atypical characteristic. Thus, the answer to both questions is no. This answer held irrespective of the threshold for classifying typical or atypical. Our results challenge the assumption that ONHs with atypical sensitivity to IOP must have atypical characteristics. This finding suggests that the traditional approach of identifying risk factors by comparing characteristics between patient groups (e.g. ocular hypertensive vs. primary open angle glaucoma) may not be a sound strategy.

Postmortem computed tomography (PMCT) and autopsy in deadly gunshot wounds--a comparative study.

INTRODUCTION: Postmortem computed tomography (PMCT) data in gunshot-related death were evaluated by two reader groups and compared to the gold standard autopsy for the determination of forensic pathology criteria. MATERIALS AND METHODS: Reader group I consisted of two board-certified radiologists whereas one board-certified radiologist and one board-certified forensic pathologist formed group II. PMCT data of 51 gunshot-related deaths were evaluated for the forensic pathology criteria number of gun shots, localization of gunshot injury, caliber, and direction of the gunshot differentiating between entry and exit wound as well as associated injury to surrounding tissue. The results of both reader groups were compared to the each other and to autopsy findings considered as gold standard. RESULTS: Reader groups I and II and as gold standard the autopsy evaluation showed in general a good correlation between all results. The overall discrepancy rate was 12/51 (23.4%) cases for group I and 8/51 (15.6%) for group II. DISCUSSION: Ultimately, the designated reader is able to draw the following conclusion from the presented data. At first, physical autopsy is better than PMCT regarding the localization of most gunshot injuries. Second, PMCT presents with better results than physical autopsy in locating fragmented bullets/fragment clouds, and finally, PMCT results of two radiologists were equivalent to the results of one evaluating radiologist and one pathologist with the exception of caliber assessment. However, referring to the pure numbers, the slight but not significant difference in the overall discrepancy rate of both reader groups might indicate the advantage of combining expertise in evaluating imaging in cases of gunshot-related death.

Paediatric CT dose: a multicentre audit of subspecialty practice in Australia and New Zealand.

OBJECTIVES: To evaluate paediatric CT dosimetry in Australia and New Zealand and calculate size-specific dose estimates (SSDEs) for chest and abdominal examinations. METHODS: Eight hospitals provided data from 12 CT systems for 1462 CTs in children aged 0-15. Imaging data were recorded for eight examinations: head (trauma, shunt), temporal bone, paranasal sinuses, chest (mass) and chest HRCT (high-resolution CT), and abdomen/pelvis (mass/inflammation). Dose data for cranial examinations were categorised by age and SSDEs by lateral dimension. Diagnostic reference ranges (DRRs) were defined by the 25th and 75th percentiles. Centralised image quality assessment was not undertaken. RESULTS: DRRs for 201 abdominopelvic SSDEs were: 2.8-4.7, 3.6-11.5, 8.5-15.0, 7.6-15, and 10.6-16.2 for the <15 cm, 15-19 cm, 20-24 cm, 25-29 cm and >30 cm groups, respectively. For 147 chest examinations using these body width categories, SSDE DRRs were 2.0-4.4, 3.3-7.9, 4.0-9.4, 4.5-12, and 6.5-12. Kilovoltage peak (kVp), but not AEC or IR, was associated with SSDE (parameter estimate [standard error]: 0.12 (0.03); p < 0.0001). CONCLUSIONS: Australian and New Zealand paediatric CT DRRs and abdominal SSDEs are comparable to international data. SSDEs for chest examinations are proposed. Dose variations could be reduced by adjusting kVp. KEY POINTS: • SSDEs can be calculated for all patients, CT systems, and practices • Kilovoltage peak (kVp) has the greatest association with dose in similar-sized patients • Paediatric DRRs for CT are now available for use internationally.

Postmortem magnetic resonance imaging of the heart ex situ: development of technical protocols.

Postmortem MRI (PMMR) examinations are seldom performed in legal medicine due to long examination times, unfamiliarity with the technique, and high costs. Furthermore, it is difficult to obtain access to an MRI device used for patients in clinical settings to image an entire human body. An alternative is available: ex situ organ examination. To our knowledge, there is no standardized protocol that includes ex situ organ preparation and scanning parameters for postmortem MRI. Thus, our objective was to develop a standard procedure for ex situ heart PMMR examinations. We also tested the oily contrast agent Angiofil® commonly used for PMCT angiography, for its applicability in MRI. We worked with a 3 Tesla MRI device and 32-channel head coils. Twelve porcine hearts were used to test different materials to find the best way to prepare and place organs in the device and to test scanning parameters. For coronary MR angiography, we tested different mixtures of Angiofil® and different injection materials. In a second step, 17 human hearts were examined to test the procedure and its applicability to human organs. We established two standardized protocols: one for preparation of the heart and another for scanning parameters based on experience in clinical practice. The established protocols enabled a standardized technical procedure with comparable radiological images, allowing for easy radiological reading. The performance of coronary MR angiography enabled detailed coronary assessment and revealed the utility of Angiofil® as a contrast agent for PMMR. Our simple, reproducible method for performing heart examinations ex situ yields high quality images and visualization of the coronary arteries.

Application of Elliptic Fourier analysis to describe the lamina cribrosa shape with age and intraocular pressure.

The lamina cribrosa (LC) plays an important biomechanical role in the optic nerve head (ONH). We developed a statistical shape model of the LC and tested if the shape varies with age or IOP. The ONHs of 18 donor eyes (47-91 years, mean 76 years) fixed at either 5 or 50 mmHg of IOP were sectioned, stained, and imaged under a microscope. A 3D model of each ONH was reconstructed and the outline of the vertical sagittal section closest to the geometric center of the LC extracted. The outline shape was described using Elliptic Fourier analysis, and principal components analysis (PCA) employed to identify the primary modes of LC shape variation. Linear mixed effect models were used to determine if the shape measurements were associated with age or IOP. The analysis revealed several modes of shape variation: thickness and depth directly (PC 1), or inversely (PC 2) related, and superior-inferior asymmetry (PC 3). Only PC 3 was associated with IOP, with higher IOP correlating with greater curvature of the LC superiorly compared to inferiorly. Our analysis enabled a concise and complete characterization of LC shape, revealing variations without defining them a priori. No association between LC shape and age was found for the relatively old population studied. Superior-inferior asymmetry of LC shape was associated with IOP, with more asymmetry at higher IOP. Increased IOP was not associated with LC thickness or depth.

A method to estimate biomechanics and mechanical properties of optic nerve head tissues from parameters measurable using optical coherence tomography.

Optic nerve head (ONH) tissue properties and biomechanics remain mostly unmeasurable in the experiment. We hypothesized that these can be estimated numerically from ocular parameters measurable in vivo with optical coherence tomography (OCT). Using parametric models representing human ONHs we simulated acute intraocular pressure (IOP) increases (10 mmHg). Statistical models were fit to predict, from OCT-measurable parameters, 15 outputs, including ONH tissue properties, stresses, and deformations. The calculations were repeated adding parameters that have recently been proposed as potentially measurable with OCT. We evaluated the sensitivity of the predictions to variations in the experimental parameters. Excellent fits were obtained to predict all outputs from the experimental parameters, with cross-validated R2s between 0.957 and 0.998. Incorporating the potentially measurable parameters improved fits significantly. Predictions of tissue stiffness were accurate to within 0.66 MPa for the sclera and 0.24 MPa for the lamina cribrosa. Predictions of strains and stresses were accurate to within 0.62% and 4.9 kPa, respectively. Estimates of ONH biomechanics and tissue properties can be obtained quickly from OCT measurements using an applet that we make freely available. These estimates may improve understanding of the eye sensitivity to IOP and assessment of patient risk for development or progression of glaucoma.

Advances in post-mortem CT-angiography.

Performing a post-mortem multidetector CT (MDCT) scan has already become routine in some institutes of forensic medicine. To better visualize the vascular system, different techniques of post-mortem CT-angiography have been explored, which can essentially be divided into partial- and whole-body angiography techniques. Probably the most frequently applied technique today is the so-called multiphase post-mortem CT-angiography (MPMCTA) a standardized method for investigating the vessels of the head, thorax and abdomen. Different studies exist, describing its use for medicolegal investigations, and its advantages as well as its artefacts and pitfalls. With the aim to investigate the performance of PMCTA and to develop and validate techniques, an international working group was created in 2012 called the "Technical Working Group Post-mortem Angiography Methods" (TWGPAM). Beyond its primary perspective, the goals of this group include creating recommendations for the indication of the investigation and for the interpretation of the images and to distribute knowledge about PMCTA. This article provides an overview about the different approaches that have been developed and tested in recent years and an update about ongoing research in this field. It will explain the technique of MPMCTA in detail and give an outline of its indications, application, advantages and limitations.

Incubation of saccharin craving and within-session changes in responding for a cue previously associated with saccharin.

Time-dependent increases in cue-induced sucrose seeking after forced abstinence have been described in rats with a history of sucrose self-administration, suggesting sucrose craving "incubates". In the present study, we examined whether the incubation of craving generalizes to the artificial sweetener, saccharin. Thirty-one male Long-Evans rats lever pressed for 0.3% saccharin solution 1h/day for 10 days. On either Day 1 or 30 of forced abstinence, rats responded for 1h for presentation of a tone+light cue previously presented with every saccharin delivery during self-administration training. Rats responded more during this cue-reactivity test session following 30 vs. 1 day of forced abstinence ("incubation of craving"). This result is the first demonstration of the "incubation of saccharin craving" and suggests that a post-ingestive caloric consequence of self-administration is not a necessary condition for the development of incubation of sucrose craving. We also examined the time course (within-session decreases) of active-lever responding during the 1-h cue-reactivity test session. Rats in the Day 30 group responded more than rats in the Day 1 group from the beginning of the test session. In addition, within-session decreases in responding were shallower in slope in the Day 30 than the Day 1 group. These results indicate that "incubation of saccharin craving" enhances the persistence of seeking behavior.

NMDA receptor subunit composition determines beta-amyloid-induced neurodegeneration and synaptic loss.

Aggregates of amyloid-beta (Aß) and tau are hallmarks of Alzheimer's disease (AD) leading to neurodegeneration and synaptic loss. While increasing evidence suggests that inhibition of N-methyl-D-aspartate receptors (NMDARs) may mitigate certain aspects of AD neuropathology, the precise role of different NMDAR subtypes for Aß- and tau-mediated toxicity remains to be elucidated. Using mouse organotypic hippocampal slice cultures from arcAß transgenic mice combined with Sindbis virus-mediated expression of human wild-type tau protein (hTau), we show that Aß caused dendritic spine loss independently of tau. However, the presence of hTau was required for Aß-induced cell death accompanied by increased hTau phosphorylation. Inhibition of NR2B-containing NMDARs abolished Aß-induced hTau phosphorylation and toxicity by preventing GSK-3ß activation but did not affect dendritic spine loss. Inversely, NR2A-containing NMDAR inhibition as well as NR2A-subunit knockout diminished dendritic spine loss but not the Aß effect on hTau. Activation of extrasynaptic NMDARs in primary neurons caused degeneration of hTau-expressing neurons, which could be prevented by NR2B-NMDAR inhibition but not by NR2A knockout. Furthermore, caspase-3 activity was increased in arcAß transgenic cultures. Activity was reduced by NR2A knockout but not by NR2B inhibition. Accordingly, caspase-3 inhibition abolished spine loss but not hTau-dependent toxicity in arcAß transgenic slice cultures. Our data show that Aß induces dendritic spine loss via a pathway involving NR2A-containing NMDARs and active caspase-3 whereas activation of eSyn NR2B-containing NMDARs is required for hTau-dependent neurodegeneration, independent of caspase-3.

[Legal considerations regarding radiological examinations of bodypackers ordered by police officers]. / Röntgenuntersuchungen von Bodypackern auf Anordnung durch Polizeibeamte.

A 28-year-old woman was arrested for body packing. One pack was removed from her vagina by the forensic pathologist. She was referred by the police to an emergency surgical department to obtain a radiological examination of the abdomen in order to rule out the presence of further packs in the intestines. In the case of a negative result it would not be necessary to be kept under arrest. For this reason the woman agrees to the examination. The surgeon in the emergency department refused to perform an examination involving radiation exposure to a young woman without any medical indications according to the German X-Ray Ordinance § 23 subsection I. Generally a physician can refuse to perform examinations ordered by state authorities; however, the provision of expert testimony in legal proceedings by a judge, a state attorney or a high ranking police officer makes collaboration mandatory in accordance with § 75 of the German penal code of procedures. However, any relevant harm caused by the examination must be excluded with a very high degree of certainty.

Active vaccination with ankyrin G reduces ß-amyloid pathology in APP transgenic mice.

Serum antibodies against amyloid-ß peptide (Aß) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in ß-amyloid plaques. Active immunization with ankG of arcAß transgenic mice reduced brain ß-amyloid pathology and increased brain levels of soluble Aß(42). AnkG immunization induced a reduction in ß-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aß-induced loss of dendritic spines in hippocampal ArcAß organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain ß-amyloid and its related neuropathology.