Pattern Of Pathological Changes Research Articles

Bombesin receptor-activated protein homolog deficiency altered the pattern of pathological changes of psoriasis - like skin lesion in mice.

This study investigated the potential role of the mouse homolog of bombesin receptor-activated protein (BRAP) in imiquimod (IMQ) induced psoriasis - like skin inflammation. The expression of both human BRAP, encoded by C6orf89, and its mouse homolog, encoded by BC004004, has been found to be expressed abundantly in the keratinocytes. BC004004 knockout mice (BC004004-/-) were topically treated with IMQ daily for 7 days to test whether they were more vulnerable to psoriasis - like inflammation. We found that those mice exhibited an altered pattern of inflammation process compared to isogenic wild type control mice (BC004004+/+). BC004004-/- mice developed skin lesions with earlier and more acute onset, as well as a quicker remission. The cytokines related to pathogenesis of psoriasis also exhibited different expression patterns in IMQ treated BC004004-/- mice. On day 4 of IMQ treatment, BC004004-/- mice exhibited a higher expression level of IL-17A compared to BC004004+/+ mice, suggesting a more robust activation of Th17 cells in the knockout mice. The serum level of thymic stromal lymphopoietin (TSLP), one of the keratinocyte derived cytokines, was also increased in BC004004-/- mice and reached its peak on day 4. Knockdown of BRAP in cultured human keratinocyte-derived HaCaT cells by siRNA silencing led to increased release of TSLP. Our data suggest that the elevated of level of TSLP released from keratinocytes due to BRAP deficiency might mediate the crosstalk between the epidermal cells and immune cells and thereby contributing to the altered pathological changes observed in psoriasis - like skin lesion in knockout mice.

Dysfunction of the noradrenergic system drives inflammation, α-synucleinopathy, and neuronal loss in mouse colon.

Clinical and pathological evidence revealed that α-synuclein (α-syn) pathology seen in PD patients starts in the gut and spreads via anatomically connected structures from the gut to the brain. Our previous study demonstrated that depletion of central norepinephrine (NE) disrupted brain immune homeostasis, producing a spatiotemporal order of neurodegeneration in the mouse brain. The purpose of this study was 1) to determine the role of peripheral noradrenergic system in the maintenance of gut immune homeostasis and in the pathogenesis of PD and 2) to investigate whether NE-depletion induced PD-like α-syn pathological changes starts from the gut. For these purposes, we investigated time-dependent changes of α-synucleinopathy and neuronal loss in the gut following a single injection of DSP-4 (a selective noradrenergic neurotoxin) to A53T-SNCA (human mutant α-syn) over-expression mice. We found DPS-4 significantly reduced the tissue level of NE and increased immune activities in gut, characterized by increased number of phagocytes and proinflammatory gene expression. Furthermore, a rapid-onset of α-syn pathology was observed in enteric neurons after 2 weeks and delayed dopaminergic neurodegeneration in the substantia nigra was detected after 3-5 months, associated with the appearance of constipation and impaired motor function, respectively. The increased α-syn pathology was only observed in large, but not in the small, intestine, which is similar to what was observed in PD patients. Mechanistic studies reveal that DSP-4-elicited upregulation of NADPH oxidase (NOX2) initially occurred only in immune cells during the acute intestinal inflammation stage, and then spread to enteric neurons and mucosal epithelial cells during the chronic inflammation stage. The upregulation of neuronal NOX2 correlated well with the extent of α-syn aggregation and subsequent enteric neuronal loss, suggesting that NOX2-generated reactive oxygen species play a key role in α-synucleinopathy. Moreover, inhibiting NOX2 by diphenyleneiodonium or restoring NE function by salmeterol (a β2-receptor agonist) significantly attenuated colon inflammation, α-syn aggregation/propagation, and enteric neurodegeneration in the colon and ameliorated subsequent behavioral deficits. Taken together, our model of PD shows a progressive pattern of pathological changes from the gut to the brain and suggests a potential role of the noradrenergic dysfunction in the pathogenesis of PD.

Patterns of structural and functional changes in the retina and choroid in acute posterior multifocal placoid pigment epitheliopathy

The study analyzes the patterns of pathological changes in the retina and choroid in acute posterior multifocal placoid pigmented epitheliopathy (APMPPE). The results of the examination of two patients with bilateral APMPPE were analyzed retrospectively. The examination had included visometry, tonometry, static perimetry, autofluorescence, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The analysis revealed signs of the inflammatory nature of the choriocapillary vascular wall lesion with the development of their local obstruction and, consequently, local ischemia of the retinal pigment epithelium (RPE) and the outer layers of the retina in the acute period. At the same time, partial destruction of the ellipsoid zone, uneven hyperreflectivity of the RPE with local areas of its elevation and impaired connection with photoreceptors were revealed. The subsequent restoration of choriocapillaris perfusion was accompanied by significant restoration of the functional and structural state of the RPE over a larger area, as well as partial restoration of the ellipsoid zone of the retina. Two years after the onset of the disease, separate areas of defects of the RPE and the outer retina were observed, coinciding in localization with zones of severe circulatory deficiency at the level of choriocapillaris in the acute stage. According to the results of multimodal imaging, choriocapillaritis is the initial link in the pathogenesis of APMPPE. The change in RPE and the outer retina is secondary to the local ischemic zones due to choriocapillaris nonperfusion. The nature of RPE change over a larger area manifests as a functional structural disorder, with the potential for recovery in case of choriocapillaris reperfusion.

Анализ нарушений связывания кортикостероидов с белками плазмы крови в патогенезе острой лучевой болезни

The study of violations of the binding of corticosteroids to blood plasma proteins in acute radia-tion syndrome allows us to clarify the mechanisms and patterns of pathological changes in the hormonal level of the body in the pathogenesis of acute radiation sickness. The relevance of the study is determined by the current risks of new man-made disasters and the threat to radiation safety. The results of the study make it possible to expand a number of theoretical positions of radiobiology on the main regularities of the binding of corticosteroids to blood plasma proteins, taking into account its various fractions, which make it possible to determine the role of free corticoids in the hormonal effect in acute radiation sickness. The purpose of this work is to study the main patterns of binding of corticosteroids to blood plasma proteins in the pathogenesis of acute radiation sickness in animals. The experiments were carried out on 20 male rabbits and 475 outbred rats. Previously experimental animals were adapted to the conditions of the experiment. The total gamma-irradiation of animals was carried out on the EGO-2 unit at an average dose rate of 575 R/min. Rabbits were irradiated at a dose of 8 Gy, rats at a dose of 8,5 Gy. The total content of 11-OCS was determined by the fluorimetric method in the author's modification. The amount of free corticosteroids was determined by the difference in their content in whole plasma and in its pro-tein fraction after separation on Sephadex G-25. Results have been obtained demonstrating changes in the fractional composition of 11-OCS in blood plasma in the pathogenesis of acute radiation sickness in animals with mono- and biphasic curves of adrenocortical response to irra-diation. Disturbances in the binding of corticosteroids to blood plasma proteins were found, resulting in an increase in free, biologically active hormones in the midst of radiation sickness. The presence in the blood plasma of non-protein-bound and therefore more mobile steroids can cause a hypercorticoid state with normal or even reduced levels of hormones in the blood. The long-term effect of "hidden" hypercortisolism, therefore, may be a factor that aggravates the clinical course of acute radiation sickness.

An observational descriptive study of pattern of pathological changes in liver in context of medico-legal autopsy done at J. L.N. Hospital, Ajmer

AI Publications is an open access peer review international journal to publish the article in the field of Agriculture, Horticulture, Food science, Rural Development, Environment and Health Research, Chemistry, Mathematics,Physics.

Light optical and Ultrastructural Characteristics of the Maral Liver with Chronic Dicrocoeliasis

BACKGROUND: Dicrocoeliasis is caused by trematode Dicrocoelium lanceatum from the family Dicrocoeliidae, a parasite in the bile ducts of the liver of domestic and wild animals. Dicrocoeliasis mainly affects sheep, cattle, camels, zebu, deer, fallow deer, argali, less often – horses, donkeys, dogs, rabbits, hares and bears, as well as humans. Dicrocoeliasis of ruminants is widespread across the whole Kazakhstan. Invasive diseases represent a significant obstacle in the development of domestic maral breeding, among which trematodoses, and particularly dicrocoeliasis of maral play a major role. AIM: The aim of the research was to study the influence of dicrocoelia on the ultrastructural organization of the liver of maral. MATERIALS AND METHODS: For examination under electron microscope, biopsy pieces of liver tissue of maral were fixed in 2.5% solution of glutaraldehyde with post-fixation in 1% solution of osmium tetroxide, conducted according to a conventional method, and enclosed in epon. Semi-thin and ultra-thin sections were prepared on the ultra-microtome Leica. Semi-thin sections were stained with methylene blue, azure 2, and studied at a high-resolution light optical level. The ultra-thin sections were contrasted with uranyl acetate and lead citrate according Reynolds method and examined under electron microscope Libra 120 (C. Zeiss). RESULTS: The light optical examination of half-thin sections revealed that the morphological pattern of pathological changes in liver tissue was polymorphic, even within a single hepatic lobe. CONCLUSIONS: In the liver of maral infected with chronic dicrocoeliasis, dystrophic and destructive pathological changes developed in all the cellular structures of the hepatic lobules: In the form of plethora and vast enlargement of sinusoids, vacuolar and lipodegeneration of hepatocytes, destruction of the hepatic tissue with edema, hemorrhages, in the appearance of cells associated with inflammation, and the deposition of hematin crystals.

Fatal pulmonary arterial thrombosis in a COVID-19 patient, with asymptomatic history, occurred after swab negativization

BackgroundA considerable number of SARS-CoV-2 infected individuals could be asymptomatic and don’t need medical treatment. The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic cases, medium-intensity forms with mild to moderate symptoms, to severe ones with bilateral pneumonia and respiratory distress. In cases with severe presentation of SARS-CoV-2 infection, the induction of hypercoagulability is one of the pathophysiological mechanism that can contribute to death.Case presentationHere, we reported autoptic evidences of thrombotic pulmonary arterial fatal lesions in an asymptomatic COVID-19 patient, after swab negativization. Whole body complete post-mortem examination was performed, showing the presence of a large thrombus occluding the main pulmonary artery that was the cause of death. Histopathological analysis showed heterogeneous pattern of pathological changes in the lung tissue with numerous vascular thrombi, inflammatory cardiomyopathy and other histopathological modifications in kidneys, spleen and liver.ConclusionsThis study provides evidences that also asymptomatic patients may be at risk to develop thrombotic complications. An appropriate diagnostic screening for thrombotic complications and the early treatment recommendations of antithrombotic drugs could represent an important topic even in asymptomatic individuals.

Genotyping, Assessment of Virulence and Antibacterial Resistance of the Rostov Strain of Mycobacterium tuberculosis Attributed to the Central Asia Outbreak Clade.

The Central Asia Outbreak (CAO) clade is a growing public health problem for Central Asian countries. Members of the clade belong to the narrow branch of the Mycobacterium tuberculosis Beijing genotype and are characterized by multidrug resistance and increased transmissibility. The Rostov strain of M. tuberculosis isolated in Russia and attributed to the CAO clade based on PCR-assay and whole genome sequencing and the laboratory strain H37Rv were selected to evaluate the virulence on C57Bl/6 mice models by intravenous injection. All mice infected with the Rostov strain succumbed to death within a 48-day period, while more than half of the mice infected by the H37Rv strain survived within a 90-day period. Mice weight analysis revealed irreversible and severe depletion of animals infected with the Rostov strain compared to H37Rv. The histological investigation of lung and liver tissues of mice on the 30th day after injection of mycobacterial bacilli showed that the pattern of pathological changes generated by two strains were different. Moreover, bacterial load in the liver and lungs was higher for the Rostov strain infection. In conclusion, our data demonstrate that the drug-resistant Rostov strain exhibits a highly virulent phenotype which can be partly explained by the CAO-specific mutations.

Analysis of nonneoplastic medical renal diseases in tumor nephrectomy specimens predicting future renal function

Introduction: Nephrectomy for renal tumor leads to decline in global renal function. The pattern of pathological changes in uninvolved renal parenchyma of nephrectomy specimen is useful to predict the future renal function. Aim: The aim of the present study is to analyze the spectrum of medical renal diseases in nonneoplastic renal parenchyma of tumors nephrectomies and preexisting comorbidities to predict future renal function. Materials and Methods: A prospective study was conducted on 100 nephrectomy patients during the period from November 2015 to February 2019. Nonneoplastic renal parenchyma of nephrectomy specimens was analyzed for the presence of any pathological changes. Serum creatinine levels at preoperative and 6 months after nephrectomy were recorded. Results: Medical renal disease in uninvolved renal parenchyma detected in 52% of cases and arterionephrosclerosis (28%) followed by diabetic nephropathy (10%) was most frequently seen. Diabetes mellitus (DM) and/or hypertension (HTN) were significantly associated with increase in arteriolar hyalinosis, glomerulosclerosis, and interstitial fibrosis/tubular atrophy (P

Placental Peripartum Pathologies in Women with Preeclampsia and Eclampsia.

Objective To determine the pattern of pathological changes in placentas of preeclamptic/eclamptic parturients and its correlation with the clinical severity as well as the perinatal outcome. Methods A cross-sectional analytical study of placental pathologies in preeclamptic/eclamptic patients was performed in a blinded pattern and compared with matched normal controls. Data were analyzed using Epi-Info 2008 version 3.5.1. Results Placental pathologies were evaluated in 61 preeclamptic/eclamptic patients and in 122 controls. Of the 61 placentas, 53 (4.7%) were of preeclampsia while 8 (0.71%) were of eclampsia. Of the preeclamptic group, 14 (23%) had mild preeclampsia while 39 (63.9%) had severe preeclampsia. Infarction, haematoma, and some histological changes increased with the severity of preeclampsia (p < 0.001). When comparing placentas in eclampsia, severe preeclampsia, mild preeclampsia, and normal controls, there was respective increase in the presence of any infarction (75%, 66.7%, 35.7% vs. 12.3%) or any haematoma (100%, 100%, 71.4% vs. 35.2%), decidual arteriopathy (87.5%, 76.9%, 64.3% vs. 35.2%), cytotrophoblastic proliferation (75%, 71.8%, 42.9% vs. 25.4%), and accelerated villous maturation (75%, 69.2%, 57.1% vs. 31.1%). There was no statistically significant difference in placental calcifications, stromal oedema, stromal fibrosis, and syncytial knots. Degree of placental infarction was correlated with the fetal birth weight. The fetal birth weight with placental involvement of >10% was significant (p=0.01). Conclusion In mild or severe preeclampsia/eclampsia, placentas had significant histological signs of ischaemia and degree of placental involvement by infarction is inversely proportional to fetal birth weight. While feto-placental ratio was higher with increased severity of the disease, the mean weight was less. This trial is registered with researchregistry3503.

Study of pattern of pathological changes in liver in autopsy cases

Study of pattern of pathological changes in liver in autopsy cases

Microstructural MRI Basis of the Cognitive Functions in Patients with Spinocerebellar Ataxia Type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum. The particular atrophy pattern results in some typical clinical features mainly including motor deficits. In addition, the presence of cognitive impairments, involving language, visuospatial and executive functions, has been also shown in SCA2 patients and it is now widely accepted as a feature of the disease. The aim of the study is to investigate the microstructural patterns and the anatomo-functional substrate that could account for the cognitive symptomatology observed in SCA2 patients. In the present study, diffusion tensor imaging (DTI) based-tractography was performed to map the main cerebellar white matter (WM) bundles, such as Middle and Superior Cerebellar Peduncles, connecting cerebellum with higher order cerebral regions. Damage-related diffusivity measures were used to determine the pattern of pathological changes of cerebellar WM microstructure in patients affected by SCA2 and correlated with the patients’ cognitive scores. Our results provide the first evidence that WM diffusivity is altered in the presence of the cerebellar cortical degeneration associated with SCA2 thus resulting in a cerebello-cerebral dysregulation that may account for the specificity of cognitive symptomatology observed in patients.

Non-linear optical imaging and quantitative analysis of the pathological changes in normal and carcinomatous human colorectal muscularis

Non-linear optical (NLO) imaging based on two-photon excitation (2PE) and second harmonic generation (SHG) has been widely used to image microstructures of biomedical specimens over the last two decades. We employed NLO imaging technology to investigate the histology of normal and carcinomatous human colorectal muscularis in transverse and longitudinal views. Results show there are different patterns of pathological changes of muscularis in tissue structure and cell morphology from both views. The NLO imaging provides identical histological information as the H&E images but requires neither stain nor tissue processing. Our study indicates that NLO imaging technology shows more detailed microstructure, which is a critical complementary tool in pathological diagnosis of colorectal tumours. It suggests that NLO imaging could be a very important diagnostic tool to help pathologists realise the real time early detection of human colorectal tumours in the foreseeable future.

Bilateral effects of unilateral cerebellar lesions as detected by voxel based morphometry and diffusion imaging.

Over the last decades, the importance of cerebellar processing for cortical functions has been acknowledged and consensus was reached on the strict functional and structural cortico-cerebellar interrelations. From an anatomical point of view strictly contralateral interconnections link the cerebellum to the cerebral cortex mainly through the middle and superior cerebellar peduncle. Diffusion MRI (dMRI) based tractography has already been applied to address cortico-cerebellar-cortical loops in healthy subjects and to detect diffusivity alteration patterns in patients with neurodegenerative pathologies of the cerebellum. In the present study we used dMRI-based tractography to determine the degree and pattern of pathological changes of cerebellar white matter microstructure in patients with focal cerebellar lesions. Diffusion imaging and high-resolution volumes were obtained in patients with left cerebellar lesions and in normal controls. Middle cerebellar peduncles and superior cerebellar peduncles were reconstructed by multi fiber diffusion tractography. From each tract, measures of microscopic damage were assessed, and despite the presence of unilateral lesions, bilateral diffusivity differences in white matter tracts were found comparing patients with normal controls. Consistently, bilateral alterations were also evidenced in specific brain regions linked to the cerebellum and involved in higher-level functions. This could be in line with the evidence that in the presence of unilateral cerebellar lesions, different cognitive functions can be affected and they are not strictly linked to the side of the cerebellar lesion.

THE CEREBRAL PERFUSION OF CIRCULATION DISTURBANCES. PART II (CT- AND MRI SEMIOTICS, PATTERNS OF PATHOLOGICAL CHANGES). REVIEW

The second part of a review article devoted to a detailed consideration of the issues of diagnostic semiotics of acute disorders of cerebral circulation using CT and MR perfusion study techniques. We consider the physiological aspects of formation of the basic parameters of tissue perfusion: of cerebral blood Șow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak (TTP) contrast, as well as patterns of pathological changes in these parameters (hypo-, hyper- and aperfusion), developing in various degrees of brain ischemic damage and penumbra areas. It is noted that the improvement of MRI using for tissue classi⠇cation of perfusion-diநusion (PWI/DWI) mismatch has a better chance of primary development due to the fact that it non-radiation exposure and is not connected with the need to introduce a large contrast volume, and with the introduction of non-contrast arterial spin labeled technique (ASL). Variants of events in the dynamics of perfusion as a result of reperfusion therapy. There were discussed the problems limiting the use of perfusion techniques in clinical practice.

Changes in Liver Parenchyma of Green Frogs (Pelophylax Esculentus Complex) Under Conditions of Anthropogenic Pollution and Their Use in Monitoring of Water Bodies

Determination of the total biological effects of anthropogenic water pollution remains an important issue. Our long-term studies have shown that numerous alterations occur in the frog liver histological structure under pressure of anthropogenic pollution factor. Th e leukocyte infiltration, fat dystrophy, protein dystrophy and necrosis are well known on the mammal liver. Also we first described the rebuilding in the normal liver structure and the depletation of the fibrous tissue which are characteristic for the amphibians. Quantitative analysis of these alterations can identify significant differences in the pattern of pathological changes in the liver of the green frogs, which pick up in anthropogenically contaminated landscapes and in the clear ponds. Th is method allows quantifying the degree of biological effect of pollution.

Concussion in Chronic Traumatic Encephalopathy.

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE.

O1‐07‐05: Paired helical filaments from Alzheimer's disease brains induce the intracellular accumulation of tau in aggresomes: Novel therapeutic approaches to prevent the propagation and spreading of tau pathology

Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer's disease (AD) and tauopathies. The specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated, it propagates between neighboring neuronal cells, possibly spreading along axonal networks. In other words, misfolded aggregated tau protein released by degenerating neurons can mediate and spread toxicity to neighboring cells. We studied whether PHFs could be taken up by cells and promote the spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green-fluorescent protein tagged tau (GFP-Tau) were treated with isolated fractions of human AD-derived PHFs for 24 hours. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was made particularly evident by the perinuclear localization of aggregates and the re-distribution of vimentin intermediate filament networks and retrograde motor protein dynein. Furthermore, the content of Sarcosylinsoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. Exosome related mechanisms did not appear to be involved in the release of GFP-Tau from untreated cells. Paired helical filaments can mediate the spreading of pathological tau aggregation. Paired helical filament-mediated formation of aggresome-like bodies may be important in neurodegeneration. The evidence that cells can internalize PHFs leading to the formation of aggresome-like bodies opens new therapeutic avenues to prevent the propagation and spreading of tau pathology.

Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes

Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer disease and tauopathies. A specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated it propagates between neighboring neuronal cells, possibly spreading along the axonal network. We studied whether PHFs released from degenerating neurons could be taken up by surrounding cells and promote spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green fluorescent protein-tagged tau (GFP-Tau) were treated with isolated fractions of human Alzheimer disease-derived PHFs for 24 h. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was particularly evident by the perinuclear localization of aggregates and redistribution of the vimentin intermediate filament network and retrograde motor protein dynein. Furthermore, the content of Sarkosyl-insoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. An exosome-related mechanism did not appear to be involved in the release of GFP-Tau from untreated cells. The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, opens new therapeutic avenues to prevent propagation and spreading of tau pathology.

Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Tangle Formation, Amyloid-β, and Microglia in Alzheimer’s Disease

Pathological hallmarks of Alzheimer’s disease (AD) include senile plaques, neurofibrillary tangles (NFTs), synaptic loss, and neurodegeneration. Senile plaques are composed of amyloid-β (Aβ) and are surrounded by microglia, a primary immune effector cell in the central nervous system. NFTs are formed by the intraneuronal accumulation of hyperphosphorylated tau, and progressive synaptic and neuronal losses closely correlate with cognitive deficits in AD. Studies on responsible genes of familial AD and temporal patterns of pathological changes in brains of patients with Down’s syndrome (Trisomy 21), who invariably develop neuropathology of AD, have suggested that Aβ accumulation is a primary event that influences other AD pathologies. Although details of the interaction between AD pathologies remain unclear, experimental evidences to discuss this issue have been accumulated. In this paper, we review and discuss recent findings that link the AD pathologies to each other. Further studies on the interaction between pathologies induced in AD brain may contribute to provide deep insight into the pathogenesis of AD and to develop novel therapeutic, prophylactic, and early diagnostic strategies for AD.