A Swin Transformer and Residualnetwork Combined Model for Breast Cancer Disease Multi-Classification Using Histopathological Images

Breast cancer has become a killer of women's health nowadays.In order to exploit the potential representational capabilities of the models more comprehensively,we propose a multi-model fusion strategy.Specifically,we combine two differently structured deep learning models,ResNet101 and Swin Transformer(SwinT),with the addition of the Convolutional Block Attention Module(CBAM)attention mechanism,which makes full use of SwinT's global context information modeling ability and ResNet101's local feature extraction ability,and additionally the cross entropy loss function is replaced by the focus loss function to solve the problem of unbalanced allocation of breast cancer data sets.The multi-classification recognition accuracies of the proposed fusion model under 40X,100X,200X and 400X BreakHis datasets are 97.50%,96.60%,96.30 and 96.10%,respectively.Compared with a single SwinT model and ResNet 101 model,the fusion model has higher accuracy and better generalization ability,which provides a more effective method for screening,diagnosis and pathological classification of female breast cancer.

Wnt/β-catenin Signaling Cascades in Cardiovascular Diseases

Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast

BACKGROUND Breast cancer ranks as one of the most prevalent malignant tumors among women,significantly endangering their health and lives.While radical surgery has been a pivotal method for halting disease progression,it alone is insufficient for enhancing the quality of life for patients.AIM To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy(NAC).METHODS Employing a case-control study design,this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022.According to the Miller-Payne grading system,the pathological response,i.e.efficacy,of the NAC in the initial breast lesion after NAC was evaluated.Of these,59 patients achieved a pathological complete response(PCR),while 119 did not(non-PCR group).Ultrasound characteristics prior to NAC were compared between these groups,and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches.RESULTS In the PCR group,the incidence of posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II were significantly lower compared to the non-PCR group(P<0.05).The area under the curve values for predicting NAC efficacy using posterior echo attenuation,lesion diameter,and Alder grade were 0.604,0.603,and 0.583,respectively.Also,rates of pathological stage II,lymph node metastasis,vascular invasion,and positive Ki-67 expression were significantly lower in the PCR group(P<0.05).Logistic regression analysis identified posterior echo attenuation,lesion diameter≥2.0 cm,Alder blood flow grade≥II,pathological stage III,vascular invasion,and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients(P<0.05).CONCLUSION While ultrasound characteristics such as posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II exhibit limited predictive value for NAC efficacy,they are significantly associated with poor response to NAC in breast cancer patients.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Analysis of the Clinical Value of Immunohistochemical Testing in the Pathological Diagnosis of Breast Cancer

Objective:To investigate the clinical value of immunohistochemistry(IHC)detection in the pathological diagnosis of breast cancer.Methods:Eighty breast cancer patients admitted to Baoding No.1 Central Hospital from June 2022 to June 2023 were selected as study subjects.The samples were divided into a positive group(40 cases)and a negative group(40 cases)according to ER and PR test results.Immunohistochemistry was performed on all patients to compare the differences between the two groups in C-erbB-2 positive expression and axillary lymph node metastasis.Results:The positive expression rate of C-erbB-2 in the positive group(35.00%)was significantly lower than that in the negative group(80.00%),with a highly significant difference(P<0.001).The axillary lymph node metastasis rate in the positive group(40.00%)was significantly lower than that in the negative group(75.00%),with a significant difference(P<0.05).Conclusion:Immunohistochemical detection in breast cancer pathology enhances diagnostic accuracy,predicts prognosis,and supports personalized treatment by identifying ER,PR,and C-erbB-2.It is worth being widely adopted in clinical practice.

Comparative Study of the Effect of Shugan Shuru Granule (疏肝舒乳颗粒) on Pathology and p53 Gene Expression in Patients with Hyperplastic Disease of Breast

Objective: To study the effect of Shugan Shuru Granule (疏肝舒乳颗粒,SSG) on the p53 gene expression in patients with hyperplastic disease of breast (HDB) to indirectly explore the mechanism of SSG’s effect on HDB on the molecular pathological level. Methods: Sixty-six patients with HDB were allocated in the treated group and the control group,with the former treated with SSG and the latter not. All patients underwent breast operation and their diseased mammary tissues were cut out, sectioned, and observed under microscopy with HE staining and immunohistochemical staining, with ABC method adopted to estimate the degree of hyperplasia and p53 gene expression. The severity of HDB was classified into normal, mild, moderate and severe grades (marked as 0 to Ⅲ), according to the degree of hyperplasia in the mammary gland. Results: Hyperplasia in the control group mostly belonged to grade Ⅰ-Ⅲ before treatment, showing overgrowth of gland and proliferation of glandular epithelial cells, which were high columnar shaped, more stratified, with papillary or substantive dysplasia. While in the treated group, most belonged to grade 0-Ⅰ after SSG treatment, with proliferated gland and dysplasia recovered to normal or disappeared. The positive rate of p53 gene expression in the treated group was 9.09%, and in the control group 39.39%, comparison between the two groups showing significant difference (P<0.01), the intensity in the former was significantly weaker than that in the latter.Conclusion: SSG could not only inhibit the proliferation of mammary duct epithelia and lobuli, but also inhibit the over-expression of P53. Therefore, it could be regarded as an effective remedy for treatment of HDB and prevention of mammary cancer genesis.

Lamotrigine protects against cognitive deficits,synapse and nerve cell damage,and hallmark neuropathologies in a mouse model of Alzheimer’s disease

Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular mechanisms remain unclear.In this study,amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice were used as a model of Alzheimer’s disease.Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months.The cognitive functions of animals were assessed using Morris water maze.Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay.The cell damage in the brain was investigated using hematoxylin and eosin staining.The levels of amyloid-βand the concentrations of interleukin-1β,interleukin-6 and tumor necrosis factor-αin the brain were measured using enzyme-linked immunosorbent assay.Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction.We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice;alleviated damage to synapses and nerve cells in the brain;and reduced amyloid-βlevels,tau protein hyperphosphorylation,and inflammatory responses.High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer’s disease-related neuropathologies may have been mediated by the regulation of Ptgds,Cd74,Map3k1,Fosb,and Spp1 expression in the brain.These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer’s disease.Furthermore,these data indicate that LTG may be a promising therapeutic drug for Alzheimer’s disease.

Correlation of MRI-determined small bowel Crohn’s disease categories with medical response and surgical pathology

AIM: To determine whether magnetic resonance imaging (MRI) can be used to categorize small bowel Crohn's disease (SB CD) into groups that correlate with response to medical therapy and surgical pathology.METHODS: Data was collected from all patients with MRI evidence of SB CD without significant colonic disease over a 32-mo period. Two radiologists, blinded to clinical findings, evaluated each MRI and grouped them based on bowel wall thickness and wall enhancement. These categories were: (1) "fibrosis", (2) "mild segmental hyper-enhancement and mild wall thickening", (3) "mild segmental hyper-enhancement and marked wall thickening", (4) "marked segmental transmural hyper-enhancement". Patient response to additional medical therapy post-MRI was prospectively determined at 8-wk. Non-responders underwent endoscopy and were offered therapeutic endoscopy or surgery. Surgical pathology was assessed against the MRI category. RESULTS: Fifty-five patients were included. Females and category "2" patients were more likely, and patients with luminal narrowing and hold-up less likely, to respond to medical therapy (P < 0.05). Seventeen patients underwent surgery. The surgical pathologicalfindings of fibrosis and the severity of inflammation correlated with the MRI category in all cases.CONCLUSION: Our fi ndings suggest that SB CD can be grouped by the MRI f indings and that these groups are associated with patients more likely to respond to continued medical therapy. The MRI categories also correlated with the presence and level of intestinal inflammation and fibrosis on surgical pathology, and may be of prognostic use in the management of CD patients.

Primary Screening for Breast Diseases among 17618 Women in Wufeng Area, a Region with High Incidence of Cervical Cancer in China

In this study, the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated. From March to August, 2009, 17618 women, from Wufeng area of Hubei province, China, were recruited to screen breast diseases by using breast infrared diagnostic apparatus. Other diagnostic methods, such as B-mode ultrasound, X-ray mammography, needle biopsy and pathological examination were, if necessary, used to further confirm the diagnosis. The screening showed that 5990 of 17618 cases (34.00%) had breast diseases, 5843 (33.16%) had mammary gland hyperplasia, 48 (0.27%) had breast fibroadenoma, 11 (0.06%) had breast carcinoma, and 88 (0.50%) had other breast diseases. The peak morbidity of breast cancer was found in the women aged 50–60 ages. The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8, 0.157%) in comparison with that in the subjects younger than 50 years old (n=3, 0.024%) (u=2.327, P<0.05). It was shown that the occurrence of breast diseases was concentrated in women aged 20–40 years, while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40. Compared with the patients elder than or equal to 40 years old (n=3289, 27.46%), the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases, 47.18%; P<0.001). However, there was no significant difference in the morbidity of breast diseases between the age group of 20–29 years and that of 30–39 years (P=0.453), and both of them were high. There was no significant association between the morbidity of breast diseases and cervical cancer. Since the morbidity of breast diseases was higher among young women, more attention should be paid to the screening of breast diseases among young women for early diagnosis.

Profiling neuroprotective potential of trehalose in animal models of neurodegenerative diseases:a systematic review

Trehalose,a unique nonreducing crystalline disaccharide,is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging,intrinsic mutations,or autophagy dysregulation.This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders(tau pathology,synucleinopathy,polyglutamine tract,and motor neuron diseases).All animal studies on neurodegenerative diseases treated with trehalose published in Medline(accessed via EBSCOhost)and Scopus were considered.Of the 2259 studies screened,29 met the eligibility criteria.According to the SYstematic Review Center for Laboratory Animal Experiment(SYRCLE)risk of bias tool,we reported 22 out of 29 studies with a high risk of bias.The present findings support the purported role of trehalose in autophagic flux and protein refolding.This review identified several other lesser-known pathways,including modifying amyloid precursor protein processing,inhibition of reactive gliosis,the integrity of the blood-brain barrier,activation of growth factors,upregulation of the downstream antioxidant signaling pathway,and protection against mitochondrial defects.The absence of adverse events and improvements in the outcome parameters were observed in some studies,which supports the transition to human clinical trials.It is possible to conclude that trehalose exerts its neuroprotective effects through both direct and indirect pathways.However,heterogeneous methodologies and outcome measures across the studies rendered it impossible to derive a definitive conclusion.Translational studies on trehalose would need to clarify three important questions:1)bioavailability with oral administration,2)optimal time window to confer neuroprotective benefits,and 3)optimal dosage to confer neuroprotection.

Dynamic Pathology and Antigen Location Study on Broiler Breeders with Coinfection of Marek's Disease Virus and Reticuloendotheliosis Virus

To further understand the generation and development of coinfection of Marek＇s disease virus （MDV） and reticuloendotheliosis virus （REV） in broiler breeders, and then find the method and optimal time of differential diagnosis for complex clinic multiple infection, the authors studied the pathohistological changes, apoptosis, immunohistochemistry （immunofluorescence）, and ultrastructure of tumor tissues of broiler breeders inoculated with MDV and REV. The study showed that proliferation of small lymphocytes was seen in the main organs at the age of 1 week, then immature lymphocytes, all kinds of lymphocytes, primitive reticulum cells, and Marek＇s disease cells （MDCs） were observed at 2-9 weeks. Apoptosis of lymphocytes could not be seen until the age of 10 weeks in the immune system. Immunohistochemistry detection showed that the positive signs of MDV and REV antigen were observed in the main organs at 2 weeks of age. Multi-morphology lymphocytes, MDV, and REV, mitotic figures and apoptosis of lymphocytes were observed with the help of transmission electron microscopy. MDV cooperating with REV promotes the course of disease of coinfection. Differential diagnosis can be done by immunohistochemistry in the early stage （before 2 weeks）, and histopathology in the late stage （post 4 weeks）. MDCs, primitive reticulum cells, immature lymphocytes, and two kinds of virions can serve as a basis for bistopathology differential diagnosis.

Putative roles of cathepsin B in Alzheimer's disease pathology: the good, the bad, and the ugly in one?

Alzheimer＇s disease（AD）is a fatal progressive neurodegenerative disorder characterized by loss in memory,cognition,and executive function and activities of daily living.AD pathogenesis has been shown to involve loss of neurons and synapses,cholinergic deficits,amyloid-beta protein（Aβ）deposition,tau protein hyperphosphorylation, and neuroinflammation.

Epidemiological Pattern of Breast Diseases among Females in the South-Western Region, Saudi Arabia

Background: Breast diseases cover several conditions. The majority of breast diseases are noncancerous. Some of these lesions are clinically unremarkable, which needed minimal intervention. However, some symptoms may be of clinical value and attract the attention of both the patient and the attending physician, especially when they become persistent. The study aimed to assess the prevalence, pattern, types, and clinical profile of breast diseases among females in the South-western region, during the period from 2018-2020. Methods: A retrospective record-based descriptive approach was used through reviewing medical records of all cases with breast disease attended King Khalid Hospital during the period from January 2018 to January 2020. Data extracted throng pre-structured questionnaire. Results: The study included 211 cases whose ages ranged from 18 to 58 years old with a mean age of 28.9 ± 12.8 years. Breast mass was the most recorded complaint (95.1%) followed with breast pain (32%), skin changes. Benign findings based on the final pathology report were recorded for more than two thirds of the cases, with the most common finding were fibroadenoma. Excisional biopsy and modified radical mastectomy were the most reported surgical interventions. Conclusions: In conclusion, the study revealed that the majority of the cases had benign breast disease (BBD), where fibroadenoma was the most frequent.

Cerebellar pathology in motor neuron disease:neuroplasticity and neurodegeneration

Amyotrophic lateral sclerosis is a relentlessly progressive multi-system condition.The clinical picture is dominated by upper and lower motor neuron degeneration,but extra-motor pathology is increasingly recognized,including cerebellar pathology.Post-mortem and neuroimaging studies primarily focus on the chara cterization of supratentorial disease,des pite emerging evidence of cerebellar degeneration in amyotrophic lateral sclerosis.Cardinal clinical features of amyotrophic lateral sclerosis,such as dysarthria,dysphagia,cognitive and behavioral deficits,saccade abnormalities,gait impairment,respiratory weakness and pseudobulbar affect are likely to be exacerbated by co-existing cerebellar pathology.This review summarizes in vivo and post mortem evidence for cerebellar degeneration in amyotrophic lateral scle rosis.Structural imaging studies consistently capture cerebellar grey matter volume reductions,diffusivity studies readily detect both intra-cerebellar and cerebellar peduncle white matter alte rations and functional imaging studies commonly report increased functional connectivity with supratentorial regions.Increased functional connectivity is commonly interpreted as evidence of neuro plasticity representing compensatory processes despite the lack of post-mortem validation.There is a scarcity of post-mortem studies focusing on cerebellar alte rations,but these detect pTDP-43 in cerebellar nuclei.Ce rebellar pathology is an overloo ked facet of neurodegeneration in amyotrophic lateral sclerosis despite its contribution to a multitude of clinical symptoms,wides p read connectivity to spinal and supratentorial regions and putative role in compensating for the degeneration of primary motor regions.

The Epidemiological, Clinical and Radiological (Echography, Mammography) Characteristics of Breast Pathologies at the Diagnostic Imaging Center (C.I.D) “Teriya” in Bamako

Breast pathology is varied, bringing together tumor and non-tumor lesions. Objective: To study the contribution of the ultrasound-mammography pair in the diagnosis of breast pathologies. Materials and Method: This was a retrospective descriptive study, carried out over a period of 3 years (from January 2018 to December 2020) at the Diagnostic Imaging Center (C.I.D) “TERIYA” in BAMAKO. It concerned all patients who came for a mammogram/ultrasound examination of the breast. All women admitted for mammogram or breast ultrasound who were diagnosed with a breast injury during the study period were included. Incomplete records and radiological checks were not included. The variables analyzed were age, sex, clinical data, and ultrasound and mammography aspects. The devices used are: a Voluson 730 PRO ultrasound machine and a G 600T type mammography machine. Results: At the end of our study, we collected 254 breast pathologies on a number of 382 women, i.e. a frequency of 66.49%. The average age of our patients was 41 years old. The dominant clinical data were mastodynia (41.88%) and mammary nodule (21.70%). On imaging (mammo-ultrasound) the lesions predominated on the left in 36% of cases, bilateral in 28% of cases and in the upper-outer quadrants in 31.5% of cases. Tumor pathologies represented 66.54% of which 45.27% were benign mainly composed of fibro-adenoma (20.88%) and cyst (18.50%), 11.8% of suspected cases and 9.45% of cancers. Non-tumor pathologies represented 33.46%, mainly mastitis (16.14%), galactophoric dilations (11.02%) and abscesses (5.51%). These pathologies were classified in 50.3% in ACR2, 17.75% in ACR3 and 4, and in 14.20% in ACR5. Lymphadenopathy was present in 73.21% of cases.

Soluble alpha-synuclein post-translational modifications:unexpected regulators of pathological alpha-synuclein amplification

The build-up of misfoldedα-synuclein(α-syn)in the central nervous system is the pathological hallmark of a number of neurodegenerative diseases that are known asα-synucleinopathies.These include Parkinson’s disease(PD),Parkinson’s disease with dementia(PDD),dementia with Lewy body(LB),multiple system atrophy(MSA),and a subset of Alzheimer’s disease.Growing evidence underscores that the intercellular transmission and amplification of pathologicalα-syn are critical processes underlying the progression ofα-synucleinopathies(Peng et al.,2020),and as such,the study of these processes could lead to the identification of promising therapeutics to mitigate disease progression.Most previous studies have focused solely on pathological seeds in relation to disease progression.

Advances in understanding and managing celiac disease:Pathophysiology and treatment strategies

In this editorial,we comment on an article published in the recent issue of the World Journal of Gastroenterology.Celiac disease(CeD)is a disease occurring in genetically susceptible individuals,which is mainly characterized by gluten intolerance in the small intestine and clinical symptoms such as abdominal pain,diarrhea,and malnutrition.Therefore,patients often need a lifelong gluten-free diet,which greatly affects the quality of life and expenses of patients.The gold standard for diagnosis is intestinal mucosal biopsy,combined with serological and genetic tests.At present,the lack of safe,effective,and satisfactory drugs for CeD is mainly due to the complexity of its pathogenesis,and it is difficult to find a perfect target to solve the multi-level needs of patients.In this editorial,we mainly review the pathological mechanism of CeD and describe the current experimental and improved drugs for various pathological aspects.

Anal Pathologies: What Management at the Reference Health Center of Bamako’s Commune V?

Anal pathologies are conditions affecting the anal margin and the anal canal. The aim of our study was to update data on anal diseases. Non-specific, it can reveal an emergency, a serious illness, a chronic disease or a benign condition. It was a prospective, descriptive and analytical study from April 2022 to March 2023, carried out in the hepato-gastroenterology unit of the Centre de Santé de Référence de la commune V du District de Bamako in Mali. Out of seven hundred and forty-nine (749) patients seen in consultation, 98 had anal pathology, i.e. a prevalence of 13.08%. The mean age was 40 ± 15.15 years and the sex ratio was 1.5. Hemorrhoidal disease and anal fissure were the most frequent pathologies in 66.4% and 24.4% of cases respectively. Medical treatment was initiated in 91.9% of patients with hemorrhoidal disease and 91.7% with anal fissure. Anal pathologies are common in young male patients. In our context, they are dominated by benign conditions.

Analysis of Alzheimer’s Disease:From Pathological Mechanism to Therapeutic Approach in Autophagy

As a“non-curable”disease,Alzheimer’s disease(AD)is the most common neurodegenerative disease in the aged population.Physical and mental pain exerts on every AD patient and their families.Even though there is no worldwide approved treatment against AD now,researchers have never given up on investigating and exploring potential approaches for curing AD.Gene therapy and drug treatment arise for alleviating AD symptoms.This paper illustrates the pathological mechanism of AD and focuses on the role of autophagy in AD pathology.Autophagy is a self-degrading mechanism to clear out dysfunctional cells;abnormal autophagy can directly trigger AD.This paper summarizes the effective and novel therapeutic approaches to treating AD by promoting autophagy activity,as well as AD diagnosis and assessment from early to severe stage,which provides promising approaches for researchers who are interested in AD treatments and feasible directions for science translational medicine.

Developing a better mouse model of Alzheimer disease with clinically relevant phenotypes in tau pathology

OBJECTIVE Transgenic mouse model has been widely used in pathogenesis study and preclinical drug evaluation in Alzheimer disease(AD).However,key differences are found between current animal models and clinical AD patients regarding phenotypes.Lack of complete models that recapitulate broad spectrum of human AD neuropathology restricts efficacy of research projects and leads to frequent failure in AD drug development at clinical trial stages.This study aims to develop better mouse models of AD through modifying key phenotype insufficiency.METHODS By crossing different single and double transgenic mice with different mutations of APP/PS1 or tau and under prion,Thy1 or PDGF-β promoter,as well as selected knockout mice,I produced a dozen of bigenic models for neuropathology screening.Further neurochemical,behavioral and pharmacological validations were conducted in the optimized mouse model.RESULTS Neuropathology phenotyping found remarkable differences in tau pathology and neurodegeneration among individual APP/PS1/tau transgenic models.I had identified a triple mouse model named FADT that showed(1) huge mature tau pathology in hippocampus and cortex;(2) abundant tau truncation,as seen in human AD brain;(3)progressive neurodegeneration;(4)selective brain atrophy in hippocampus and entorhinal cortex;(5) reproducible and late onset spatial memory defects,etc.Importantly,remarkable tau pathology in this FADT model is mainly driven by beta-amyloid pathology,which differs from high expression of tau in rTg4510 model.CONCLUSION I had developed a new triple transgenic mouse model that recapitulates broad spectrum of human AD neuropathology features.This study will not only establish a solid model basis for AD pathophysiology investigation and drug development,but also reveal important clues on the interaction of beta-amyloid and tau pathologies in the brain.