Alzheimer's disease (AD), the leading cause of dementia, is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. This condition casts a significant shadow on global health due to its complex and multifactorial nature. In addition to genetic predispositions, the development of AD is influenced by a myriad of risk factors, including aging, systemic inflammation, chronic health conditions, lifestyle, and environmental exposures. Recent advancements in understanding the complex pathophysiology of AD are paving the way for enhanced diagnostic techniques, improved risk assessment, and potentially effective prevention strategies. These discoveries are crucial in the quest to unravel the complexities of AD, offering a beacon of hope for improved management and treatment options for the millions affected by this debilitating disease.
Alzheimer Disease/metabolism* ; Humans ; Animals ; Plaque, Amyloid/metabolism* ; Risk Factors

Objective To analyze the risk factors and build a clinical prediction model for hemodynamic depression (HD) after carotid artery stenting (CAS). Methods A total of 116 patients who received CAS in the Department of Vascular Surgery,Drum Tower Clinical College of Nanjing Medical University and the Department of Vascular Surgery,the Affiliated Suqian First People's Hospital of Nanjing Medical University from January 1,2016 to January 1,2022 were included in this study.The patients were assigned into a HD group and a non-HD group.The clinical baseline data and vascular disease characteristics of each group were collected,and multivariate Logistic regression was employed to identify the independent predictors of HD after CAS and build a clinical prediction model.The receiver operating characteristic (ROC) curve was drawn,and the area under the ROC curve (AUC) was calculated to evaluate the predictive performance of the model. Results The HD group had lower proportions of diabetes (P=0.014) and smoking (P=0.037) and higher proportions of hypertension (P=0.031),bilateral CAS (P=0.018),calcified plaque (P=0.001),eccentric plaque (P=0.003),and the distance<1 cm from the minimum lumen level to the carotid bifurcation (P=0.009) than the non-HD group.The age,sex,coronary heart disease,symptomatic carotid artery stenosis,degree of stenosis,and length of lesions had no statistically significant differences between the HD group and the non-HD group (all P>0.05).Based on the above predictive factors,a clinical prediction model was established,which showed the AUC of 0.807 and the 95% CI of 0.730-0.885 (P<0.001).The model demonstrated the sensitivity of 62.7% and the specificity of 87.7% when the best cut-off value of the model score reached 12.5 points. Conclusions Diabetes,smoking,calcified plaque,eccentric plaque,and the distance<1 cm from the minimum lumen level to the carotid bifurcation are independent predictors of HD after CAS.The clinical prediction model built based on the above factors has good performance in predicting the occurrence of HD after CAS.
Humans ; Carotid Stenosis ; Depression ; Models, Statistical ; Prognosis ; Stents ; Hemodynamics ; Plaque, Amyloid

Amyloid beta (Aβ) plaques are one of the hallmarks of Alzheimer's disease (AD). However, currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans. It has been found that there are different types of Aβ plaque (diffuse and focal types) in the postmortem human brain. In this study, we aimed to investigate the correlations among different types of Aβ plaque and AD-related neuropathological and cognitive changes based on a postmortem human brain bank in China. The results indicated that focal plaques, but not diffuse plaques, significantly increased with age in the human hippocampus. We also found that the number of focal plaques was positively correlated with the severity of AD-related neuropathological changes (measured by the "ABC" scoring system) and cognitive decline (measured by the Everyday Cognitive Insider Questionnaire). Furthermore, most of the focal plaques were co-localized with neuritic plaques (identified by Bielschowsky silver staining) and accompanied by microglial and other inflammatory cells. Our findings suggest the potential of using focal-type but not general Aβ plaques as biomarkers for the neuropathological evaluation of AD.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor ; Brain/pathology* ; Cognitive Dysfunction/pathology* ; Hippocampus/metabolism* ; Humans ; Neuroinflammatory Diseases ; Plaque, Amyloid/pathology*

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia worldwide, and is mainly characterized by aggregated β-amyloid (Aβ). Increasing evidence has shown that plant extracts have the potential to delay AD development. The plant sterol β-Sitosterol has a potential role in inhibiting the production of platelet Aβ, suggesting that it may be useful for AD prevention. In the present study, we aimed to investigate the effect and mechanism of β-Sitosterol on deficits in learning and memory in amyloid protein precursor/presenilin 1 (APP/PS1) double transgenic mice. APP/PS1 mice were treated with β-Sitosterol for four weeks, from the age of seven months. Brain Aβ metabolism was evaluated using ELISA and Western blotting. We found that β-Sitosterol treatment can improve spatial learning and recognition memory ability, and reduce plaque load in APP/PS1 mice. β-Sitosterol treatment helped reverse dendritic spine loss in APP/PS1 mice and reversed the decreased hippocampal neuron miniature excitatory postsynaptic current frequency. Our research helps to explain and support the neuroprotective effect of β-Sitosterol, which may offer a novel pharmaceutical agent for the treatment of AD. Taken together, these findings suggest that β-Sitosterol ameliorates memory and learning impairment in APP/PS1 mice and possibly decreases Aβ deposition.
Alzheimer Disease ; Amyloid ; Animals ; Blood Platelets ; Blotting, Western ; Brain ; Cognition Disorders ; Dementia ; Dendritic Spines ; Enzyme-Linked Immunosorbent Assay ; Excitatory Postsynaptic Potentials ; Learning ; Memory ; Metabolism ; Mice ; Mice, Transgenic ; Neurodegenerative Diseases ; Neurons ; Neuroprotective Agents ; Plant Extracts ; Plants ; Plaque, Amyloid ; Spatial Learning

BACKGROUND AND PURPOSE: In Alzheimer's continuum (a comprehensive of preclinical Alzheimer's disease [AD], mild cognitive impairment [MCI] due to AD, and AD dementia), cognitive dysfunctions are often related to cortical atrophy in specific brain regions. The purpose of this study was to investigate the association between anatomical pattern of cortical atrophy and specific neuropsychological deficits. METHODS: A total of 249 participants with Alzheimer's continuum (125 AD dementia, 103 MCI due to AD, and 21 preclinical AD) who were confirmed to be positive for amyloid deposits were collected from the memory disorder clinic in the department of neurology at Samsung Medical Center in Korea between September 2013 and March 2018. To analyze neuropsychological test-specific neural correlates representing the relationship between cortical atrophy measured by cortical thickness and performance in specific neuropsychological tests, a linear regression analysis was performed. Two neural correlates acquired by 2 different standardized scores in neuropsychological tests were also compared. RESULTS: Cortical atrophy in several specific brain regions was associated with most neuropsychological deficits, including digit span backward, naming, drawing-copying, verbal and visual recall, semantic fluency, phonemic fluency, and response inhibition. There were a few differences between 2 neural correlates obtained by different z-scores. CONCLUSIONS: The poor performance of most neuropsychological tests is closely related to cortical thinning in specific brain areas in Alzheimer's continuum. Therefore, the brain atrophy pattern in patients with Alzheimer's continuum can be predict by an accurate analysis of neuropsychological tests in clinical practice.
Alzheimer Disease ; Atrophy ; Brain ; Cognition ; Dementia ; Humans ; Korea ; Linear Models ; Memory Disorders ; Mild Cognitive Impairment ; Neuroanatomy ; Neurology ; Neuropsychological Tests ; Plaque, Amyloid ; Semantics

The link of diabetes with co-occurring disorders in the brain involves complex and multifactorial pathways. Genetically engineered rodents that express familial Alzheimer's disease-associated mutant forms of amyloid precursor protein and presenilin 1 (PSEN1) genes provided invaluable insights into the mechanisms and consequences of amyloid deposition in the brain. Adding diabetes factors (obesity, insulin impairment) to these animal models to predict success in translation to clinic have proven useful at some extent only. Here, we focus on contributing factors to diabetic brain injury with the aim of identifying appropriate animal models that can be used to mechanistically dissect the pathophysiology of diabetes-associated cognitive dysfunction and how diabetes medications may influence the development and progression of cognitive decline in humans with diabetes.
Amyloid ; Brain Injuries ; Brain ; Dementia ; Diabetes Mellitus ; Humans ; Insulin ; Models, Animal ; Obesity ; Plaque, Amyloid ; Presenilin-1 ; Rodentia

Alzheimer's Disease (AD) is a progressive neurodegenerative disease, which is pathologically defined by the accumulation of amyloid plaques and hyper-phosphorylated tau aggregates in the brain. Mitochondrial dysfunction is also a prominent feature in AD, and the extracellular Aβ and phosphorylated tau result in the impaired mitochondrial dynamics. In this study, we generated an induced pluripotent stem cell (iPSC) line from an AD patient with amyloid precursor protein (APP) mutation (Val715Met; APP-V715M) for the first time. We demonstrated that both extracellular and intracellular levels of Aβ were dramatically increased in the APP-V715M iPSC-derived neurons. Furthermore, the APP-V715M iPSC-derived neurons exhibited high expression levels of phosphorylated tau (AT8), which was also detected in the soma and neurites by immunocytochemistry. We next investigated mitochondrial dynamics in the iPSC-derived neurons using Mito-tracker, which showed a significant decrease of anterograde and retrograde velocity in the APP-V715M iPSC-derived neurons. We also found that as the Aβ and tau pathology accumulates, fusion-related protein Mfn1 was decreased, whereas fission-related protein DRP1 was increased in the APP-V715M iPSC-derived neurons, compared with the control group. Taken together, we established the first iPSC line derived from an AD patient carrying APP-V715M mutation and showed that this iPSC-derived neurons exhibited typical AD pathological features, including a distinct mitochondrial dysfunction.
Alzheimer Disease ; Amyloid ; Brain ; Carisoprodol ; Humans ; Immunohistochemistry ; Mitochondrial Dynamics ; Neurites ; Neurodegenerative Diseases ; Neurons ; Pathology ; Plaque, Amyloid ; Pluripotent Stem Cells

Diagnostic guidelines for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease (AD) were released by the National Institute on Aging and Alzheimer's Association (NIA-AA) in 2011. Promoted by the subsequent scientific progress, a unifying update, the ‘NIA-AA Research Framework', was published in 2018. This new research framework shifts the definition of AD from syndrome to biological construct based on biomarkers in living people. The biomarkers were grouped into β amyloid deposition (A), pathologic tau (T), and neurodegeneration (N) related, termed the ‘AT(N) classification system#x2019;, which could be extended with new biomarkers as they become available in the future. For the staging of cognitive impairment, three syndromal stages for observational studies and six numeric stages for clinical trials were also suggested. This biomarker-based classification combined with clinical staging is expected to enhance the understanding of AD as well as aid in precise targeting for interventional clinical trials. This review focused on the introduction of the new 2018 NIA-AA Research Framework. Although this framework has been proposed for research purposes, it is expected to be adopted into general clinical practice with thorough examination and validation in the future.
Alzheimer Disease ; Biomarkers ; Classification ; Cognition Disorders ; Dementia ; Mild Cognitive Impairment ; National Institute on Aging (U.S.) ; Plaque, Amyloid

PURPOSE: To report a case of primary amyloidosis localized to the conjunctiva. CASE SUMMARY: A 19-year-old male with a conjunctival mass and foreign body sensations in the right eye transferred from another hospital. A 0.5 × 2.5 cm reddish mass was present in the medial canthus of the right conjunctiva with no other clinically specific signs. Surgical excisional biopsy was performed. Histological examination showed amyloid deposition. There was no other orbital involvement apart from the conjunctiva. Abnormalities were not found in the systemic examination. CONCLUSIONS: We report a case of primary amyloidosis localized to the conjunctiva.
Amyloidosis ; Biopsy ; Conjunctiva ; Conjunctival Neoplasms ; Foreign Bodies ; Humans ; Lacrimal Apparatus ; Male ; Orbit ; Plaque, Amyloid ; Sensation ; Young Adult

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) may be the first symptomatic stage of Alzheimer's disease (AD). Hence, a screening tool to characterize the patients' complaints and assess the risk of AD is required. We investigated the SCD neuroimaging biomarker distributions and the relevance between the self-report questionnaire and Alzheimer's pathologic changes. METHODS: Individuals aged 50 and above with consistent cognitive complaints without any objective cognitive impairments were eligible for the study. The newly developed questionnaire consisted of 2 parts; 10 questions translated from the ‘SCD-plus criteria’ and a Korean version of the cognitive failure questionnaire by Broadbent. All the subjects underwent physical examinations such as blood work, detailed neuropsychological tests, the self-report questionnaire, brain magnetic resonance imagings, and florbetaben positron emission tomography (PET) scans. Amyloid PET findings were interpreted using both visual rating and quantitative analysis. Group comparisons and association analysis were performed using SPSS (version 18.0). RESULTS: A total of 31 participants with SCD completed the study and 25.8% showed positive amyloid depositions. The degree of periventricular white matter hyperintensities (WMH) and hippocampal atrophy were more severe in amyloid-positive SCDs compared to the amyloid-negative group. In the self-reported questionnaire, the ‘informant's report a decline’ and ‘symptom's onset after 65 years of age’ were associated with more Alzheimer's pathologic changes. CONCLUSIONS: Amyloid-positive SCDs differed from amyloid-negative SCDs on WMH, hippocampal atrophy, and a few self-reported clinical features, which gave clues on the prediction of AD pathology.
Alzheimer Disease ; Amyloid ; Atrophy ; Biomarkers ; Brain ; Cognition Disorders ; Mass Screening ; Neuroimaging ; Neuropsychological Tests ; Pathology ; Physical Examination ; Plaque, Amyloid ; Positron-Emission Tomography ; White Matter