- Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease. [Journal Article]Nat Neurosci. 2023 Feb 06 [Online ahead of print]NN
- Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD is unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is upregulated predominantly by perivascular macrophages and, to a lesser extent, by periv…
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- Near-infrared fluorescence lifetime imaging of amyloid-β aggregates and tau fibrils through the intact skull of mice. [Journal Article]Nat Biomed Eng. 2023 Feb 06 [Online ahead of print]NB
- Non-invasive methods for the in vivo detection of hallmarks of Alzheimer's disease can facilitate the study of the progression of the disease in mouse models and may enable its earlier diagnosis in humans. Here we show that the zwitterionic heptamethine fluorophore ZW800-1C, which has peak excitation and emission wavelengths in the near-infrared optical window, binds in vivo and at high contrast …
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- Osteocalcin ameliorates cognitive dysfunctions in a mouse model of Alzheimer's Disease by reducing amyloid β burden and upregulating glycolysis in neuroglia. [Journal Article]Cell Death Discov. 2023 Feb 06; 9(1):46.CD
- Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by the accumulation of amyloid β peptides (Aβ) and impaired glucose metabolism in the brain. Osteocalcin (OCN), an osteoblast-derived protein, has been shown to modulate brain functions but whether it has any effect on AD is undetermined. In this study, daily intraperitoneal injection of OCN for 4 weeks ameliorate…
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- Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress. [Journal Article]Life Sci Alliance. 2023 Apr; 6(4)LS
- NLRP3 is a pattern recognition receptor with a well-documented role in inducing inflammasome assembly in response to cellular stress. Deregulation of its activity leads to many inflammatory disorders including gouty arthritis, Alzheimer disease, and cancer. Whereas its role in the context of cancer has been mostly explored in the immune compartment, whether NLRP3 exerts functions unrelated to imm…
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- DOPA pheomelanin is increased in nigral neuromelanin of Parkinson's disease. [Journal Article]Prog Neurobiol. 2023 Feb 04 [Online ahead of print]PN
- Neuromelanin (NM) in dopaminergic neurons of human substantia nigra (SN) has a melanic component that consists of pheomelanin and eumelanin moieties and has been proposed as a key factor contributing to dopaminergic neuron vulnerability in Parkinson's disease (PD). While eumelanin is considered as an antioxidant, pheomelanin and related oxidative stress are associated with compromised drug and me…
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- Blood Biomarkers of Neuronal/Axonal and Glial Injury in Human Immunodeficiency Virus-Associated Neurocognitive Disorders. [Journal Article]Dement Geriatr Cogn Disord. 2023 Feb 06 [Online ahead of print]DG
- CONCLUSIONS: Our data suggest that neuronal degeneration (as evidenced by increased levels of NfL), but not tau pathology or glial degeneration, is related to cognitive status in PLWH. Our results corroborate the view that blood NfL is a promising biomarker of cognitive impairment in PLWH.
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- Transcriptional activation of CSTB gene expression by transcription factor Sp3. [Journal Article]Biochem Biophys Res Commun. 2023 Jan 30; 649:71-78.BB
- CSTB has been reported to be associated with the pathogenesis of many malignant tumors, especially hepatocellular carcinoma (HCC). However, how the expression of this gene is regulated is largely unknown. We initially cloned and analyzed the promoter region of the CSTB gene by luciferase assay and the Sp3 binding site (CCCCGCCCCGCG) was found in it. The results of electrophoretic mobility shift a…
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- An attention-based deep learning approach for the classification of subjective cognitive decline and mild cognitive impairment using resting-state EEG. [Journal Article]J Neural Eng. 2023 Feb 06 [Online ahead of print]JN
- Objective. This study aims to design and implement the first Deep Learning (DL) model to classify subjects in the prodromic states of Alzheimer's Disease (AD) based on resting-state electroencephalographic signals.Approach. EEG recordings of 17 Healthy Controls (HC), 56 Subjective Cognitive Decline (SCD) and 45 Mild Cognitive Impairment (MCI) subjects were acquired at resting state. After preproc…
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- Structural Proteomic Profiling of Cerebrospinal Fluids to Reveal Novel Conformational Biomarkers for Alzheimer's Disease. [Journal Article]J Am Soc Mass Spectrom. 2023 Feb 06 [Online ahead of print]JA
- Alzheimer's disease (AD) is the most common representation of dementia, with brain pathological hallmarks of protein abnormal aggregation, such as with amyloid beta and tau protein. It is well established that posttranslational modifications on tau protein, particularly phosphorylation, increase the likelihood of its aggregation and subsequent formation of neurofibrillary tangles, another hallmar…
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- Brain aerobic glycolysis and resilience in Alzheimer disease. [Journal Article]Proc Natl Acad Sci U S A. 2023 Feb 14; 120(7):e2212256120.PN
- The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aβ) deposition in individuals with symptomatic and preclinical Alzheimer disease (AD). Brain AG decreases with age, but the functional significance of this decrease with regard to the development of AD symptomatology is poorly understood. Using PET measurements of regional blood flow, …
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- Investigation of the gait parameters after donepezil treatment in patients with alzheimer' s disease. [Journal Article]Appl Neuropsychol Adult. 2023 Feb 06 [Online ahead of print]AN
- CONCLUSIONS: Our results support the efficiency of cholinergic treatment in gait functions in AD subjects.
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- Changes in Alcohol Consumption and Risk of Dementia in a Nationwide Cohort in South Korea. [Journal Article]JAMA Netw Open. 2023 Feb 01; 6(2):e2254771.JN
- CONCLUSIONS: In this cohort study of a Korean population, decreased risk of dementia was associated with maintaining mild to moderate alcohol consumption, reducing alcohol consumption from a heavy to a moderate level, and the initiation of mild alcohol consumption, suggesting that the threshold of alcohol consumption for dementia risk reduction is low.
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- Prediction of Longitudinal Cognitive Decline in Preclinical Alzheimer Disease Using Plasma Biomarkers. [Journal Article]JAMA Neurol. 2023 Feb 06 [Online ahead of print]JN
- CONCLUSIONS: In this study, plasma P-tau217 predicted cognitive decline in patients with preclinical AD. These findings suggest that plasma P-tau217 may be used as a complement to CSF or PET for participant selection in clinical trials of novel disease-modifying treatments.
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- Establishing the Validity and Reliability of an Online Motor Learning Game: Applications for Alzheimer's Disease Research Within MindCrowd. [Journal Article]Games Health J. 2023 Feb 06 [Online ahead of print]GH
- Objective: Motor practice effects (i.e., improvements in motor task performance with practice) are emerging as a unique variable that can predict Alzheimer's disease (AD) progression and biomarker positivity. However, the tasks used to study motor practice effects have involved face-to-face assessment, making them difficult to integrate into large internet-based cohorts that represent the next ge…
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- Integrated use of ligand and structure-based virtual screening, molecular dynamics, free energy calculation and ADME prediction for the identification of potential PTP1B inhibitors. [Journal Article]Mol Divers. 2023 Feb 06 [Online ahead of print]MD
- Protein tyrosine phosphatases (PTPs) are the group of enzymes that control both cellular activity and the dephosphorylation of tyrosine (Tyr)-phosphorylated proteins. Dysregulation of PTP1B has contributed to numerous diseases including Diabetes Mellitus, Alzheimer's disease, and obesity rendering PTP1B as a legitimate target for therapeutic applications. It is highly challenging to target this e…
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- Traversing through the cell signaling pathways of neuroprotection by betanin: therapeutic relevance to Alzheimer's Disease and Parkinson's Disease. [Review]Metab Brain Dis. 2023 Feb 06 [Online ahead of print]MB
- Modulation of cell signaling pathways is the key area of research towards the treatment of neurodegenerative disorders. Altered Nrf2-Keap1-ARE (Nuclear factor erythroid-2-related factor 2-Kelch-like ECH-associated protein 1-Antioxidant responsive element) and SIRT1 (Sirtuin 1) cell signaling pathways are considered to play major role in the etiology and pathogenesis of Alzheimer's disease (AD) an…
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- How does neurokinin 3 receptor agonism affect pathological and cognitive impairments in an Alzheimer's disease-like rat model? [Journal Article]Amino Acids. 2023 Feb 06 [Online ahead of print]AA
- Alzheimer's disease (AD) is accepted as a form of progressive dementia. Cholinergic systems are commonly affected in AD. Neurokinin 3 receptor (NK3R) is involved in learning memory-related processes. It is known that the activation of NK3R affects the release of many neurotransmitters. The aim of this project was to investigate the effects of NK3R agonist senktide administration on neurobehaviora…
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- Focused ultrasound: Innovation in use for neurologic conditions. [Journal Article]Trauma Emerg Med. 2022; 1(1):1-12.TE
- Focused ultrasound has emerged as a key tool for neurologic disorders. In this focused review, we discuss the utility in disrupting the blood brain barrier to maximize treatment. This can facilitate creating direct coagulative lesions and aid in the administration of chemotherapy. Furthermore, it can facilitate neuromodulation when used in pulse sequencing. The current literature regarding brain …
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- Digital Intervention For The Management Of Alzheimer's Disease. [Journal Article]Curr Alzheimer Res. 2023 Feb 06 [Online ahead of print]CA
- Alzheimer's disease (AD) is a progressive, multifactorial, chronic, neurodegenerative disease with high prevalence and limited therapeutic options, making it a global health crisis. Being the most common cause of dementia, AD erodes the cognitive, functional, and social abilities of the individual and causes escalating medical and psychosocial needs. As yet, this disorder has no cure and current …
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- Pesticide exposure and Alzheimer's disease: A case-control study. [Journal Article]Curr Alzheimer Res. 2023 Feb 06 [Online ahead of print]CA
- CONCLUSIONS: Therefore, it may conclude that pesticides, at least in part, contribute to AD development through several mechanisms, including the induction of oxidative stress.
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- Sense of Purpose in Life and Beliefs and Knowledge of Alzheimer's Disease. [Journal Article]Arch Clin Neuropsychol. 2023 Feb 04 [Online ahead of print]AC
- CONCLUSIONS: Individuals with a sense of purpose are less concerned about risk of developing ad and believe modifiable factors reduce risk. These beliefs may support engagement in behaviors that reduce risk and be one psychological pathway through which purpose protects against ad.
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- Association of Influenza Vaccination and Dementia Risk: A Meta-Analysis of Cohort Studies. [Journal Article]J Alzheimers Dis. 2023 Feb 03 [Online ahead of print]JA
- CONCLUSIONS: Influenza vaccination in older adults was markedly associated with a decreased risk of dementia. More mechanistic studies and epidemiological studies are needed to clarify the association between influenza vaccination and decreased dementia risk.
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- PSA-NCAM Regulatory Gene Expression Changes in the Alzheimer's Disease Entorhinal Cortex Revealed with Multiplexed in situ Hybridization. [Journal Article]J Alzheimers Dis. 2023 Feb 01 [Online ahead of print]JA
- CONCLUSIONS: We conclude that PSA-NCAM dysregulation may cause subsequent loss of structural plasticity in AD, and this may result from a loss of PST mRNA expression. Due PSTs involvement in structural plasticity, intervention for AD may be possible by targeting this disrupted plasticity pathway.
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- Effect of Metabolic Syndrome Risk Factors on Processing Speed and Executive Function in Three Racialized Groups. [Journal Article]J Alzheimers Dis. 2023 Feb 03 [Online ahead of print]JA
- CONCLUSIONS: Metabolic dysfunction incrementally affects cognitive trajectory, with generally similar associations across racial groups. Since racialized groups exhibit higher levels of both MetS and ADRD, MetS may represent a driving factor for increased ADRD risk experience by racialized group and an important and modifiable target through which to reduce risk of ADRD.
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- Urinary Amino Acid-Conjugated Acrolein and Taurine as New Biomarkers for Detection of Dementia. [Journal Article]J Alzheimers Dis. 2023 Jan 28 [Online ahead of print]JA
- CONCLUSIONS: Since urine is relatively easy to collect, our findings provide a novel biomarker for dementia without invasiveness.
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- Impaired Early Insulin Response to Glucose Load Predicts Episodic Memory Decline: A 10-Year Population-Based Cohort Follow-Up of 45-74-Year-Old Men and Women. [Journal Article]J Alzheimers Dis. 2023 Jan 28 [Online ahead of print]JA
- CONCLUSIONS: Our results suggest that decreased early insulin secretion predicts episodic memory decline in middle-aged to elderly men and women.
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- Accumulation of pTau231 at the Postsynaptic Density in Early Alzheimer's Disease. [Journal Article]J Alzheimers Dis. 2023 Jan 30 [Online ahead of print]JA
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- Regional White Matter Hyperintensities and Alzheimer's Disease Biomarkers Among Older Adults with Normal Cognition and Mild Cognitive Impairment. [Journal Article]J Alzheimers Dis. 2023 Jan 28 [Online ahead of print]JA
- CONCLUSIONS: These findings suggest that although WMH are primarily related to systemic vascular risk and neurodegeneration (i.e., t-tau), AD-specific pathways may contribute to the formation of WMH in a regionally-specific manner, with neurofibrillary tangles (i.e., p-tau) playing a role in temporal WMHs and amyloid (i.e., Aβ 42/Aβ 40) in parietal WMHs.
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- Progression from Prodromal Alzheimer's Disease to Mild Alzheimer's Disease Dementia in the Verubecestat APECS Study: Adjudicating Diagnostic Transitions. [Journal Article]J Alzheimers Dis. 2023 Jan 28 [Online ahead of print]JA
- CONCLUSIONS: A positive Site Investigator opinion is an excellent predictor for a positive adjudication decision regarding onset of dementia. Conversely, sole use of CDR sum-of-boxes change ≥2 is inadequate. The benefit of centralized adjudication appears doubtful.
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- Soluble TREM2, Alzheimer's Disease Pathology, and Risk for Progression of Cerebral Small Vessel Disease: A Longitudinal Study. [Journal Article]J Alzheimers Dis. 2023 Jan 28 [Online ahead of print]JA
- BackgroundUntil recently, studies on associations between neuroinflammation in vivo and cerebral small vessel disease (CSVD) are scarce. Cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a candidate biomarker of microglial activation and neuroinflammation, were found elevated in Alzheimer's disease (AD), but they have not been fully explored in…
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