Morphofunctional Investigation in a Transgenic Mouse Model of Alzheimer's Disease: Non-Reactive Astrocytes Are Involved in Aß Load and Reactive Astrocytes in Plaque Build-Up.

The term neuroinflammation defines the reactions of astrocytes and microglia to alterations in homeostasis in the diseased central nervous system (CNS), the exacerbation of which contributes to the neurodegenerative effects of Alzheimer's disease (AD). Local environmental conditions, such as the presence of proinflammatory molecules, mechanical properties of the extracellular matrix (ECM), and local cell-cell interactions, are determinants of glial cell phenotypes. In AD, the load of the cytotoxic/proinflammatory amyloid ß (Aß) peptide is a microenvironmental component increasingly growing in the CNS, imposing time-evolving challenges on resident cells. This study aimed to investigate the temporal and spatial variations of the effects produced by this process on astrocytes and microglia, either directly or by interfering in their interactions. Ex vivo confocal analyses of hippocampal sections from the mouse model TgCRND8 at different ages have shown that overproduction of Aß peptide induced early and time-persistent disassembly of functional astroglial syncytium and promoted a senile phenotype of reactive microglia, hindering Aß clearance. In the late stages of the disease, these patterns were altered in the presence of Aß-plaques, surrounded by typically reactive astrocytes and microglia. Morphofunctional characterization of peri-plaque gliosis revealed a direct contribution of astrocytes in plaque buildup that might result in shielding Aß-peptide cytotoxicity and, as a side effect, in exacerbating neuroinflammation.

Basal Ganglia Compensatory White Matter Changes on DTI in Alzheimer's Disease.

The volume reduction of the gray matter structures in patients with Alzheimer's disease is often accompanied by an asymmetric increase in the number of white matter fibers located close to these structures. The present study aims to investigate the white matter structure changes in the motor basal ganglia in Alzheimer's disease patients compared to healthy controls using diffusion tensor imaging. The amounts of tracts, tract length, tract volume, quantitative anisotropy, and general fractional anisotropy were measured in ten patients with Alzheimer's disease and ten healthy controls. A significant decrease in the number of tracts and general fractional anisotropy was found in patients with Alzheimer's disease compared to controls in the right caudate nucleus, while an increase was found in the left and the right putamen. Further, a significant decrease in the structural volume of the left and the right putamen was observed. An increase in the white matter diffusion tensor imaging parameters in patients with Alzheimer's disease was observed only in the putamen bilaterally. The right caudate showed a decrease in both the diffusion tensor imaging parameters and the volume in Alzheimer's disease patients. The right pallidum showed an increase in the diffusion tensor imaging parameters but a decrease in volume in Alzheimer's disease patients.

The first description of dermal armour in snakes.

Osteoderms, also called dermal armour, often play a role in predator defence. The presence of osteoderms is highly irregularly distributed across the squamate phylogeny and they have not been found in snakes. In this study, we searched for candidate snake species that would benefit from such armour to protect their body, focusing primarily on fossorial species with defensive tail displays. We examined the tail morphology of 27 snake species from different families using micro-computed tomography (µCT) and micro- radiography. We discovered dermal armour in four species of sand boas (Erycidae) that also feature enlarged and highly modified caudal vertebrae. This is the first description of dermal armour in snakes. Ancestral state reconstructions revealed that osteoderms likely evolved once or multiple times in Erycidae. We have not found osteoderms in any other examined snake species. Nevertheless, similar structures are known from unrelated squamate clades, such as gerrhosaurids and geckos. This supports the idea of underlying deep developmental homology. We propose the hypothesis that osteoderms protect sand boas like the "brigandine armour" of medieval warriors. We interpret it as another component of the sand boas' rich defence strategy.

Morphology of Anterior Cingulate Cortex and Its Relation to Schizophrenia.

Cortical folding of the anterior cingulate cortex (ACC), particularly the cingulate (CS) and the paracingulate (PCS) sulci, represents a neurodevelopmental marker. Deviations in in utero development in schizophrenia can be traced using CS and PCS morphometry. In the present study, we measured the length of CS, PCS, and their segments on T1 MRI scans in 93 patients with first- episode schizophrenia and 42 healthy controls. Besides the length, the frequency and the left-right asymmetry of CS/PCS were compared in patients and controls. Distribution of the CS and PCS morphotypes in patients was different from controls. Parcellated sulcal pattern CS3a in the left hemisphere was longer in patients (53.8 ± 25.7 mm vs. 32.7 ± 19.4 mm in controls, p < 0.05), while in CS3c it was reversed­longer in controls (52.5 ± 22.5 mm as opposed to 36.2 ± 12.9 mm, n.s. in patients). Non parcellated PCS in the right hemisphere were longer in patients compared to controls (19.4 ± 10.2 mm vs. 12.1 ± 12.4 mm, p < 0.001). Therefore, concurrent presence of PCS1 and CS1 in the left hemisphere and to some extent in the right hemisphere may be suggestive of a higher probability of schizophrenia.

A Three-Arm Parallel-group Exploratory Trial documents balance improvement without much evidence of white matter integrity changes in people with multiple sclerosis following two months ambulatory neuroproprioceptive "facilitation and inhibition" physical therapy.

BACKGROUND: Changes of white matter integrity in people with multiple sclerosis (MS) were documented following mainly motor/skill acquisitions physical therapy, while following neuroproprioceptive "facilitation, inhibition" (neurofacilitation) only by two pilot studies. Neurofacilitation has potential to induce white matter changes due to the possibility of interfering with the neuronal tactility threshold. However stronger evidence is missing. AIM: This study investigates whether neurofacilitation (three physical therapy types) induce white matter changes and if they relate to clinical improvement. DESIGN: The Three-Arm Parallel-group Exploratory Trial (NCT04355663). SETTING: Each group underwent different kinds of two months ambulatory therapy (Motor Program Activating Therapy, Vojta's reflex locomotion and Functional Electric Stimulation in Posturally Corrected Position). POPULATION: MS people with moderate disability. METHODS: At baseline and after the program, participants underwent magnetic resonance diffusion tensor imaging (DTI) and clinical assessment. Fractional anisotropy maps obtained from DTI were further analyzed using tract-based spatial statistic exploring the mean values in the whole statistic skeleton. Moreover, additional exploratory analysis in 48 regions of white matter was done. RESULTS: Ninety-two people were recruited. DTI data from 61 people were analyzed. The neurofacilitation (irrespective type of therapy) resulted in significant improvement on the Berg Balance Scale (P=0.0089), mainly driven by the Motor Program Activating Therapy. No statistically significant change in the whole statistic skeleton was observed (only a trend for decrement of fractional anisotropy after Vojta's reflex locomotion). Additional exploratory analysis confirmed significant decrement of fractional anisotropy in the right anterior corona radiata. CONCLUSIONS: Neurofacilitation improved balance without much evidence of white matter integrity changes in people with MS. CLINICAL REHABILITATION IMPACT: The study results point to the importance of neuroproprioceptive "facilitation and inhibition" physical therapy in the management of balance in people with multiple sclerosis; and the potential to induce white matter changes due to the possibility of interfering with the neuronal tactility threshold.

Determinate growth is predominant and likely ancestral in squamate reptiles.

Body growth is typically thought to be indeterminate in ectothermic vertebrates. Indeed, until recently, this growth pattern was considered to be ubiquitous in ectotherms. Our recent observations of a complete growth plate cartilage (GPC) resorption, a reliable indicator of arrested skeletal growth, in many species of lizards clearly reject the ubiquity of indeterminate growth in reptiles and raise the question about the ancestral state of the growth pattern. Using X-ray micro-computed tomography (µCT), here we examined GPCs of long bones in three basally branching clades of squamate reptiles, namely in Gekkota, Scincoidea and Lacertoidea. A complete loss of GPC, indicating skeletal growth arrest, was the predominant finding. Using a dataset of 164 species representing all major clades of lizards and the tuataras, we traced the evolution of determinate growth on the phylogenetic tree of Lepidosauria. The reconstruction of character states suggests that determinate growth is ancestral for the squamate reptiles (Squamata) and remains common in the majority of lizard lineages, while extended (potentially indeterminate) adult growth evolved several times within squamates. Although traditionally associated with endotherms, determinate growth is coupled with ectothermy in this lineage. These findings combined with existing literature suggest that determinate growth predominates in both extant and extinct amniotes.

Computer Kinesiology: New Diagnostic and Therapeutic Tool for Lower Back Pain Treatment (Pilot Study).

The aim of this study was to demonstrate the effectiveness of the diagnostic and therapeutic medical information system Computer Kinesiology in physiotherapy in patients with low back pain who were not responding to conventional therapy. Computer Kinesiology is primarily intended for the diagnostics and therapy of functional disorders of the locomotor system. This pilot study population included 55 patients (Group 1) with acute and chronic back pain and 51 persons (Group 2) without back pain. The third group was a control group of 67 healthy volunteers with no evidence of musculoskeletal pathologies and no back pain. All 173 subjects were examined three times by the diagnostic part of the Computer Kinesiology method. Groups 1 and 2 were treated after every diagnostics. Group 3 was not treated. The effect was evaluated by H score. Improvements after therapy were defined by reducing the H score by at least 1 point. In Group 1, the H score decreased by at least 1 point in 87.3% (95% CI: 75.5-94.7) and in Group 2 in 78.4% (95% CI: 64.7-88.7). There was no change of distribution of H Score grade in Group 3. The improvement neither depended on gender, age, and BMI nor was it influenced by the length of the therapy. This study demonstrated a high therapeutic efficacy of the Computer Kinesiology system in patients with back pain (Group 1) and in persons without back pain (Group 2) who used the Computer Kinesiology system for primary and secondary prevention of back pain.

Vascular supply of the anterior interventricular epicardial nerves and ventricular Purkinje fibers in the porcine hearts.

The aim of this study was to perform a pilot histological and quantitative analysis of the blood vessels accompanying the epicardial nerves (vasa nervorum) in the porcine hearts. Twenty healthy porcine hearts were used in this study. The blood vessels were analyzed by light microscopy using four different staining techniques in transverse sections taken from the upper, middle, and lower segments of the anterior part of the interventricular region and the adjacent parts of the right and left ventricles containing epicardial nerves and the endocardial peripheral parts of the Purkinje fibers. In total, 317 epicardial nerves were detected. The vasa nervorum were present in 75.7% of these nerves. The vasa nervorum resembled arterioles and postcapillary and collecting venules. One hundred and forty nine epicardial nerves were perivascular, located in the adventitia of the anterior interventricular artery and vein. The remaining 168 nerves ran freely through the epicardial interstitium. The presence of the vasa nervorum was not related to topographical location or nerve diameter. Additionally, from a total of 33 analyzed ventricular complexes of Purkinje fibers small blood vessels located in their proximity were identified in only two cases. It can be concluded that the majority of the anterior epicardial nerves of porcine heart possess well-developed vasa nervorum. In contrast, similar blood vessels are rarely present in the vicinity of the Purkinje fibers. The data obtained contribute to a better understanding of the nutrition of the cardiac nerves.

Universality of indeterminate growth in lizards rejected: the micro-CT reveals contrasting timing of growth cartilage persistence in iguanas, agamas, and chameleons.

Squamate reptiles are considered to exhibit indeterminate growth. Nevertheless, current literature disputes the available definitions of this growth type, presents new theoretical models, and questions its universality in cold-blooded vertebrates. We have followed up on our previous research employing micro-CT to explore growth plate cartilage (GPC) in the epiphysis of long bones, which is responsible for longitudinal skeletal growth by the endochondral ossification process. We focused on numerous and highly diversified group of the Iguania clade comprising Acrodonta (agamas and chameleons) and Pleurodonta ("iguanas"). We recorded the absence of GPC in most of the examined adult Pleurodonta specimens and interpret it as an irreversible arrest of skeletal growth. This finding clearly rejects the universality of indeterminate growth in lizards. On the other hand, we found apparent GPC preservation in most of the adult specimens belonging to Acrodonta. This suggests a preserved ability to continue body growth throughout most of their life. We discuss the uncovered disparity between Acrodonta and Pleurodonta and emphasize the importance of GPC degradation timing.

New Design of the Electrophoretic Part of CLARITY Technology for Confocal Light Microscopy of Rat and Human Brains.

BACKGROUND: CLARITY is a method of rendering postmortem brain tissue transparent using acrylamide-based hydrogels so that this tissue could be further used for immunohistochemistry, molecular biology, or gross anatomical studies. Published papers using the CLARITY method have included studies on human brains suffering from Alzheimer's disease using mouse spinal cords as animal models for multiple sclerosis. METHODS: We modified the original design of the Chung CLARITY system by altering the electrophoretic flow-through cell, the shape of the platinum electrophoresis electrodes and their positions, as well as the cooling and recirculation system, so that it provided a greater effect and can be used in any laboratory. RESULTS: The adapted CLARITY system is assembled from basic laboratory components, in contrast to the original design. The modified CLARITY system was tested both on rat brain stained with a rabbit polyclonal anti-Iba-1 for microglial cells and on human nucleus accumbens stained with parvalbumin and tyrosine hydroxylase for visualization of specific neurons by confocal laser scanning microscopy. CONCLUSIONS: Our design has the advantage of simplicity, functional robustness, and minimal requirement for specialized additional items for the construction of the CLARITY apparatus.

Imaging of Mouse Brain Fixated in Ethanol in Micro-CT.

Micro-CT imaging is a well-established morphological method for the visualization of animal models. We used ethanol fixation of the mouse brains to perform high-resolution micro-CT scans showing in great details brain grey and white matters. It was possible to identify more than 50 neuroanatomical structures on the 5 selected coronal sections. Among white matter structures, we identified fornix, medial lemniscus, crossed tectospinal pathway, mammillothalamic tract, and the sensory root of the trigeminal ganglion. Among grey matter structures, we identified basal nuclei, habenular complex, thalamic nuclei, amygdala, subparts of hippocampal formation, superior colliculi, Edinger-Westphal nucleus, and others. We suggest that micro-CT of the mouse brain could be used for neurohistological lesions evaluation as an alternative to classical neurohistology because it does not destroy brain tissue.

Ethanol fixation method for heart and lung imaging in micro-CT.

PURPOSE: The soft tissue imaging in micro-CT remains challenging due to its low intrinsic contrast. The aim of this study was to create a simple staining method omitting the usage of contrast agents for ex vivo soft tissue imaging in micro-CT. MATERIALS AND METHODS: Hearts and lungs from 30 mice were used. Twenty-seven organs were either fixed in 97% or 50% ethanol solution or in a series of ascending ethanol concentrations. Images were acquired after 72, 168 and 336 h on a custom-built micro-CT machine and compared to scans of three native samples. RESULTS: Ethanol provided contrast enhancement in all evaluated fixations. Fixation in 97% ethanol resulted in contrast enhancement after 72 h; however, it caused hardening of the samples. Fixation in 50% ethanol provided contrast enhancement after 336 h, with milder hardening, compared to the 97% ethanol fixation, but the visualization of details was worse. The fixation in a series of ascending ethanol concentrations provided the most satisfactory results; all organs were visualized in great detail without tissue damage. CONCLUSIONS: Simple ethanol fixation improves the tissue contrast enhancement in micro-CT. The best results can be obtained with fixation of the soft tissue samples in a series of ascending ethanol concentrations.

Difference in Subjective Accessibility of On Demand Recall of Visual, Taste, and Olfactory Memories.

We present here significant difference in the evocation capability between sensory memories (visual, taste, and olfactory) throughout certain categories of the population. As object for this memory recall we selected French fries that are simple and generally known. From daily life we may intuitively feel that there is much better recall of the visual and auditory memory compared to the taste and olfactory ones. Our results in young (age 12-21 years) mostly females and some males show low capacity for smell and taste memory recall compared to far greater visual memory recall. This situation raises question whether we could train smell and taste memory recall so that it could become similar to visual or auditory ones. In our article we design technique of the volunteers training that could potentially lead to an increase in the capacity of their taste and olfactory memory recollection.

Compensatory Shift of Subcallosal Area and Paraterminal Gyrus White Matter Parameters on DTI in Patients with Alzheimer Disease.

OBJECTIVE: Alzheimer disease is traditionally conceptualized as a disease of brain gray matter, however, studies with diffusion tensor imaging have demonstrated that Alzheimer disease also involves alterations in white matter integrity. We measured number of tracts, tracts length, tract volume, quantitative anisotropy and general fractional anisotropy of neuronal tracts in subcallosal area, paraterminal gyrus and fornix in patients with Alzheimer disease and healthy age-matched controls. Our hypothesis was that patients with Alzheimer disease should exhibit decrease in the integrity of these white matter structures that are crucial for semantic memory function. METHODS: For our study were selected 24 patients with confirmed Alzheimer disease diagnosis and 24 healthy controls (AD center, Department of Neurology, Charles University, Prague, Czech Republic). Statistically significant differences between the patients with Alzheimer disease and the control group were found both on the left and right fornices but only concerning the tract numbers and tract length. The subcallosal area and paraterminal gyrus showed statistically significant differences between the patients with Alzheimer disease and the control group, but only on the left side and only associated with the tract volume and quantitative anisotropy. CONCLUSION: Our explanation for these findings lies in the severe hippocampal atrophy (and subsequent loss of function) with compensatory hypertrophy of the subcallosal area and paraterminal gyrus neuronal fibers that occurs in Alzheimer's disease, as an adaptation to the loss of projection from the hippocampal formation via fornix.

Trans-generational neurochemical modulation of methamphetamine in the adult brain of the Wistar rat.

Chronic methamphetamine (METH) abuse has been shown to elicit strong neurotoxic effects. Yet, with an increasing number of children born to METH abusing mothers maturing into adulthood, one important question is how far do the neurotoxic effects of METH alter various neurotransmitter systems in the adult METH-exposed offspring. The purpose of this study was to investigate long-term trans-generational neurochemical changes, following prenatal METH exposure, in the adult Wistar rat brain. METH or saline (SAL-control animals) was administered to pregnant dams throughout the entire gestation period (G0-G22). At postnatal day 90, dopamine, serotonin, glutamate and GABA were measured in the adult brain before (baseline) and after a METH re-administration using in vivo microdialysis and liquid chromatography/mass spectrometry. The results show that METH-exposure increased basal levels of monoamines and glutamate, but decreased GABA levels in all measured brain regions. Acute challenge with METH injection in the METH-exposed group induced a lower increase in the monoamine system relative to the increase in the GABAergic and glutamatergic system. The data show that prenatal METH exposure has strong effects on the monoaminergic, GABAergic and glutamatergic system even when exposure to METH was limited to the prenatal phase. Toxicological effects of METH have therefore longer lasting effects as currently considered and seem to affect the excitatory-inhibitory balance in the brain having strong implications for cognitive and behavioral functioning.

Effect of stress on structural brain asymmetry.

There is a growing body of evidence that stressful events may affect the brain not only as a whole, but also in multiple laterality aspects. The present review is aimed at discussing the effect of stress and stress hormones on structural brain asymmetry. Differences and crossroads of functional and structural asymmetry are briefly mentioned throughout the document. The first part of this review summarizes major findings in the field of structural brain asymmetries in animals and humans from the evolutionary perspective. Additionally, effect of stress on animals is discussed generally. The second part then explores asymmetrical effects of stress on structural changes of principal brain areas - amygdala, hippocampus, neocortex, diencephalon, basal forebrain and basal ganglia from the point of normal lateralization, steroids, trauma and genetic factors. At the end we present hypothesis why stress appears to have asymmetrical effects on lateralized brain structures.

High-contrast X-ray micro-radiography and micro-CT of ex-vivo soft tissue murine organs utilizing ethanol fixation and large area photon-counting detector.

Using dedicated contrast agents high-quality X-ray imaging of soft tissue structures with isotropic micrometre resolution has become feasible. This technique is frequently titled as virtual histology as it allows production of slices of tissue without destroying the sample. The use of contrast agents is, however, often an irreversible time-consuming procedure and despite the non-destructive principle of X-ray imaging, the sample is usually no longer usable for other research methods. In this work we present the application of recently developed large-area photon counting detector for high resolution X-ray micro-radiography and micro-tomography of whole ex-vivo ethanol-preserved mouse organs. The photon counting detectors provide dark-current-free quantum-counting operation enabling acquisition of data with virtually unlimited contrast-to-noise ratio (CNR). Thanks to the very high CNR even ethanol-only preserved soft-tissue samples without addition of any contrast agent can be visualized in great detail. As ethanol preservation is one of the standard steps of tissue fixation for histology, the presented method can open a way for widespread use of micro-CT with all its advantages for routine 3D non-destructive soft-tissue visualisation.

Differential impact of stress on hypothalamic-pituitary-adrenal axis: gene expression changes in Lewis and Fisher rats.

The aim of the present work was to study the influence of variable stress on the expression of 11ß-hydroxysteroid dehydrogenase type 1 (11HSD1) and the neuropeptides corticotropin-releasing hormone (CRH), urocortins 2 and 3(UCN2, UCN3), arginine vasopressin (AVP), oxytocin (OXT) and adenylate cyclase-activating polypeptide (PACAP) in two inbred rat strains: stress hypo-responsive Lewis (LEW) and hyper-responsive Fisher 344 (F344) rats. We found site-specific and strain-dependent differences in the basal and stress-stimulated expression of 11HSD1, CRH, UCN2, UCN3 and PACAP. In LEW rats, stress upregulated 11HSD1 in the prefrontal cortex and lateral amygdala, whereas in F344 rats 11HSD1 was upregulated in the central amygdala and hippocampal CA2 and ventral but not dorsal CA1 region; no effect was observed in the paraventricular nucleus, pituitary gland and adrenal cortex of both strains. The expression of glucocorticoid receptors did not parallel the upregulation of 11HSD1. Stress also stimulated the expression of paraventricular OXT, CRH, UCN3 and PACAP in both strains but amygdalar CRH only in LEW and UCN2/UCN3 in F344 rats, respectively. The upregulation of PACAP and CRH was paralleled only by increased expression of PACAP receptor PAC1 but not CRH receptor type 1. These observations provide evidence that inbred F344 and LEW rats exhibit not only the well-known phenotypic differences in the activity of the HPA axis but also strain- and stress-dependent differences in the expression of genes encoding 11HSD1 and neuropeptides associated with the HPA axis activity. Moreover, the differences in 11HSD1 expression suggest different local concentration of corticosterone and access to GR in canonical and noncanonical structures of the HPA axis.

Hippocampal spatial position evaluation on MRI for research and clinical practice.

In clinical practice as well as in many volumetric studies we use different reorientations of the brain position towards x and y axis on the magnetic resonance imaging (MRI) scans. In order to find out whether it has an overall effect on the resulting 2D data, manual hippocampal area measurements and rotation variability of the brain (in two reoriented axes) and the skull were performed in 23 Alzheimer's disease patients and 31 healthy controls. After the MRI scanning, native brain scans (nat) were reoriented into the two different artificial planes (anterior commissure-posterior commissure axis (AC-PC) and hippocampal horizontal long axis (hipp)). Hippocampal area and temporal horn of the lateral ventricle was measured manually using freeware Image J program. We found that 1) hippocampal area of nat images is larger compared to hipp images, area of the nat images is equal to the AC-PC images and area of the hipp images is smaller compared to AC-PC images, 2) hippocampal area together with the area of the temporal horn for nat images is larger compared to hipp images, area of the hipp images is smaller compared to the AC-PC images and area of the nat images is smaller compared to the AC-PC images. The conclusion is that the measured area of the hippocampus in the native MRI is almost the same as the area of MRI reoriented only into the AC-PC axis. Therefore, when performing 2D area studies of the hippocampus or in the clinical practice we recommend usage of not-reoriented MRI images or to reorient them into the AC-PC axis. Surprising finding was that rotation of both AC-PC and hipp line towards x-axis among patients varies up to 35° and the same is true for the skull rotation so that it is not only a matter of the brain position.

Simple method for evaluation of planum temporale pyramidal neurons shrinkage in postmortem tissue of Alzheimer disease patients.

We measured the length of the pyramidal neurons in the cortical layer III in four subregions of the planum temporale (transitions into superior temporal gyrus, Heschl's gyrus, insular cortex, and Sylvian fissure) in control group and Alzheimer disease patients. Our hypothesis was that overall length of the pyramidal neurons would be smaller in the Alzheimer disease group compared to controls and also there would be right-left asymmetry in both the control and Alzheimer disease groups. We found pyramidal neuron length asymmetry only in controls--in the transition into the Sylvian fissure--and the rest of the subregions in the control group and Alzheimer disease patients did not show size difference. However, control-Alzheimer disease group pyramidal neuron length comparison revealed (a) no length difference in superior temporal gyrus transition area, (b) reversal of asymmetry in the insular transition area with left insular transition significantly shorter in the Alzheimer disease group compared to the control group, (c) both right and left Heschl's gyrus transitions significantly shorter in the Alzheimer disease group compared to the control group, and (d) right Sylvian fissure transition significantly shorter in the Alzheimer disease group compared to the control group. This neuronal length measurement method could supplement already existing neuropathological criteria for postmortem Alzheimer disease diagnostics.