keyword
https://read.qxmd.com/read/38494787/association-between-hippocampal-microglia-ad-and-late-nc-and-cognitive-decline-in-older-adults
#1
JOURNAL ARTICLE
Alifiya Kapasi, Lei Yu, Sue E Leurgans, Sonal Agrawal, Patricia A Boyle, David A Bennett, Julie A Schneider
INTRODUCTION: This study investigates the relationship between microglia inflammation in the hippocampus, brain pathologies, and cognitive decline. METHODS: Participants underwent annual clinical evaluations and agreed to brain donation. Neuropathologic evaluations quantified microglial burden in the hippocampus, amyloid beta (Aβ), tau tangles, and limbic age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy neuropathologic changes (LATE-NC), and other common brain pathologies...
March 17, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://read.qxmd.com/read/38493185/rejuvenating-aged-microglia-by-p16-ink4a-sirna-loaded-nanoparticles-increases-amyloid-%C3%AE-clearance-in-animal-models-of-alzheimer-s-disease
#2
JOURNAL ARTICLE
Hyo Jung Shin, In Soo Kim, Seung Gyu Choi, Kayoung Lee, Hyewon Park, Juhee Shin, Dayoung Kim, Jaewon Beom, Yoon Young Yi, Deepak Prasad Gupta, Gyun Jee Song, Won-Suk Chung, C Justin Lee, Dong Woon Kim
Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer's disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance...
March 16, 2024: Molecular Neurodegeneration
https://read.qxmd.com/read/38491393/long-term-high-fat-diet-consumption-aggravates-%C3%AE-amyloid-deposition-and-tau-pathology-accompanied-by-microglial-activation-in-an-alzheimer-s-disease-model
#3
JOURNAL ARTICLE
Zheng Liang, Xiaokang Gong, Yang Zhao, Yanna Zhao, Jing Yu, Tiantian Huang, Chaoqing Yang, Liangwei Wu, Mengbing Huang, Xiaochuan Wang, Xiji Shu, Jian Bao
Alzheimer's disease (AD) is the most prevailing form of dementia, with long-term high-fat diet (HFD) consumption being a pivotal contributor to AD pathogenesis. As microglial dysfunction is a crucial factor in the AD onset, it becomes imperative to explore the effects of HFD on microglial function and AD pathogenesis. In the present study, 3xTg-AD model mice at the age of 9-month are subjected to random allocation, with one group receiving a standard diet (ND) and the other an HFD for 3 months. Subsequently, transcriptomic profiling of microglia unveils that HFD alters fatty acid metabolism and mediates T cell infiltration...
March 15, 2024: Molecular Nutrition & Food Research
https://read.qxmd.com/read/38472715/oxidative-stress-endoplasmic-reticulum-stress-and-apoptosis-in-the-pathology-of-alzheimer-s-disease
#4
REVIEW
Bidemi Emmanuel Ekundayo, Tajudeen Olabisi Obafemi, Olusola Bolaji Adewale, Blessing Ariyo Obafemi, Babatunji Emmanuel Oyinloye, Stella Kemilola Ekundayo
Alzheimer's disease (AD) accounts for a major statistic among the class of neurodegenerative diseases. A number of mechanisms have been identified in its pathogenesis and progression which include the amyloid beta (Aβ) aggregation, hyperphosphorylation of tau protein, oxidative stress, endoplasmic reticulum (ER) stress and apoptosis. These processes are interconnected and contribute significantly to the loss of neurons, brain mass and consequential memory loss and other cognitive difficulties. Oxidative stress in AD appears to be caused by excess of oxygen free radicals and extracellular Aβ deposits that cause local inflammatory processes and activate microglia, another possible source of reactive oxygen species (ROS)...
March 12, 2024: Cell Biochemistry and Biophysics
https://read.qxmd.com/read/38469162/effects-of-early-tooth-loss-on-chronic-stress-and-progression-of-neuropathogenesis-of-alzheimer-s-disease-in-adult-alzheimer-s-model-app-nl-g-f-mice
#5
JOURNAL ARTICLE
Suzuko Ochi, Kumiko Yamada, Takashi Saito, Takaomi C Saido, Mitsuo Iinuma, Kagaku Azuma, Kin-Ya Kubo
INTRODUCTION: Alzheimer's disease (AD), the most common neurodegenerative disease, is characterized by accumulated amyloid-β (Aβ) plaques, aggregated phosphorylated tau protein, gliosis-associated neuroinflammation, synaptic dysfunction, and cognitive impairment. Many cohort studies indicate that tooth loss is a risk factor for AD. The detailed mechanisms underlying the association between AD and tooth loss, however, are not yet fully understood. METHODS: We explored the involvement of early tooth loss in the neuropathogenesis of the adult AppNL-G-F mouse AD model...
2024: Frontiers in Aging Neuroscience
https://read.qxmd.com/read/38468308/apoe4-genotype-and-aging-impair-injury-induced-microglial-behavior-in-brain-slices-including-toward-a%C3%AE-through-p2ry12
#6
JOURNAL ARTICLE
Jordy Sepulveda, Jennifer Yejean Kim, Joseph Binder, Stefano Vicini, G William Rebeck
Microglia are highly dynamic cells that play a critical role in tissue homeostasis through the surveillance of brain parenchyma and response to cues associated with damage. Aging and APOE4 genotype are the strongest risk factors for Alzheimer's disease (AD), but how they affect microglial dynamics remains unclear. Using ex vivo confocal microscopy, we analyzed microglial dynamic behaviors in the entorhinal cortex (EC) and hippocampus CA1 of 6-, 12-, and 21-month-old mice APOE3 or APOE4 knock-in mice expressing GFP under the CX3CR1 promoter...
March 11, 2024: Molecular Neurodegeneration
https://read.qxmd.com/read/38459540/characterization-of-preclinical-alzheimer-s-disease-model-spontaneous-type-2-diabetic-cynomolgus-monkeys-with-systemic-pro-inflammation-positive-biomarkers-and-developing-ad-like-pathology
#7
JOURNAL ARTICLE
Xinxin Huang, Shanshan Huang, Fangyan Fu, Junzhen Song, Yuling Zhang, Feng Yue
BACKGROUND: The key to the prevention and treatment of Alzheimer's disease (AD) is to be able to predict and diagnose AD at the preclinical or early stage, but the lack of a preclinical model of AD is the critical factor that causes this problem to remain unresolved. METHODS: We assessed 18 monkeys in vivo evaluation of pro-inflammatory cytokines and AD pathological biomarkers (n = 9 / type 2 diabetic mellitus (T2DM) group, age 20, fasting plasma glucose (FPG) ≥ 100 mg/dL, and n = 9 / negative control (NC) group, age 17, FPG < 100 mg/dL)...
March 8, 2024: Alzheimer's Research & Therapy
https://read.qxmd.com/read/38458367/targeting-aberrant-glycosylation-to-modulate-microglial-response-and-improve-cognition-in-models-of-alzheimer-s-disease
#8
JOURNAL ARTICLE
Yue Wang, Yixuan Du, Hongfei Huang, Yiming Cao, Kemeng Pan, Yueqian Zhou, Jiawei He, Wenbing Yao, Song Chen, Xiangdong Gao
Altered glycosylation profiles have been correlated with potential drug targets in various diseases, including Alzheimer's disease (AD). In this area, the linkage between bisecting N-acetylglucosamine (GlcNAc), a product of N-acetylglucosaminyltransferase III (GnT-III), and AD has been recognized, however, our understanding of the cause and the causative role of this aberrant glycosylation in AD are far from completion. Moreover, the effects and mechanisms of glycosylation-targeting interventions on memory and cognition, and novel targeting strategies are worth further study...
March 6, 2024: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/38450383/human-stem-cell-transplantation-models-of-alzheimer-s-disease
#9
REVIEW
Nkechime Ifediora, Peter Canoll, Gunnar Hargus
Alzheimer's disease (AD) is the most frequent form of dementia. It is characterized by pronounced neuronal degeneration with formation of neurofibrillary tangles and deposition of amyloid β throughout the central nervous system. Animal models have provided important insights into the pathogenesis of AD and they have shown that different brain cell types including neurons, astrocytes and microglia have important functions in the pathogenesis of AD. However, there are difficulties in translating promising therapeutic observations in mice into clinical application in patients...
2024: Frontiers in Aging Neuroscience
https://read.qxmd.com/read/38446249/glial-reactivity-in-a-mouse-model-of-beta-amyloid-deposition-assessed-by-pet-imaging-of-p2x7-receptor-and-tspo-using-11-c-smw139-and-18-f-f-dpa
#10
JOURNAL ARTICLE
Obada M Alzghool, Richard Aarnio, Jatta S Helin, Saara Wahlroos, Thomas Keller, Markus Matilainen, Junel Solis, Jonathan J Danon, Michael Kassiou, Anniina Snellman, Olof Solin, Juha O Rinne, Merja Haaparanta-Solin
BACKGROUND: P2X7 receptor has emerged as a potentially superior PET imaging marker to TSPO, the gold standard for imaging glial reactivity. [11 C]SMW139 is the most recently developed radiotracer to image P2X7 receptor. The aim of this study was to image reactive glia in the APP/PS1-21 transgenic (TG) mouse model of Aβ deposition longitudinally using [11 C]SMW139 targeting P2X7 receptor and to compare tracer uptake to that of [18 F]F-DPA targeting TSPO at the final imaging time point...
March 6, 2024: EJNMMI Research
https://read.qxmd.com/read/38442267/cholesterol-25-hydroxylase-mediates-neuroinflammation-and-neurodegeneration-in-a-mouse-model-of-tauopathy
#11
JOURNAL ARTICLE
Danira Toral-Rios, Justin M Long, Jason D Ulrich, Jinsheng Yu, Michael R Strickland, Xianlin Han, David M Holtzman, Anil G Cashikar, Steven M Paul
Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a "disease-associated microglia" signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25-HC, there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene...
April 1, 2024: Journal of Experimental Medicine
https://read.qxmd.com/read/38441695/progranulin-and-neuropathological-features-of-alzheimer-s-disease-longitudinal-study
#12
JOURNAL ARTICLE
Fardin Nabizadeh, Rasa Zafari
BACKGROUND: Progranulin is an anti-inflammatory protein that plays an essential role in the synapse function and the maintenance of neurons in the central nervous system (CNS). It has been shown that the CSF level of progranulin increases in Alzheimer's disease (AD) patients and is associated with the deposition of amyloid-beta (Aβ) and tau in the brain tissue. In this study, we aimed to assess the longitudinal changes in cerebrospinal fluid (CSF) progranulin levels during different pathophysiological stages of AD and investigate associated AD pathologic features...
March 5, 2024: Aging Clinical and Experimental Research
https://read.qxmd.com/read/38426371/genetic-diversity-promotes-resilience-in-a-mouse-model-of-alzheimer-s-disease
#13
JOURNAL ARTICLE
Neelakshi Soni, Lindsay A Hohsfield, Kristine M Tran, Shimako Kawauchi, Amber Walker, Dominic Javonillo, Jimmy Phan, Dina Matheos, Celia Da Cunha, Asli Uyar, Giedre Milinkeviciute, Angela Gomez-Arboledas, Katelynn Tran, Catherine C Kaczorowski, Marcelo A Wood, Andrea J Tenner, Frank M LaFerla, Gregory W Carter, Ali Mortazavi, Vivek Swarup, Grant R MacGregor, Kim N Green
INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder with multifactorial etiology, including genetic factors that play a significant role in disease risk and resilience. However, the role of genetic diversity in preclinical AD studies has received limited attention. METHODS: We crossed five Collaborative Cross strains with 5xFAD C57BL/6J female mice to generate F1 mice with and without the 5xFAD transgene. Amyloid plaque pathology, microglial and astrocytic responses, neurofilament light chain levels, and gene expression were assessed at various ages...
March 1, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://read.qxmd.com/read/38405339/novel-development-and-prospects-in-pathogenesis-diagnosis-and-therapy-of-alzheimer-s-disease
#14
REVIEW
Zenghui Teng
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with cognitive decline and behavioral dysfunction. AD will become a global public health concern due to its increasing prevalence brought on by the severity of global aging. It is critical to understand the pathogenic mechanisms of AD and investigate or pursue a viable therapy strategy in clinic. Amyloid-β (Aβ) accumulation and abnormally hyperphosphorylated tau protein are the main regulating variables in the pathological phase of AD...
2024: JAD Reports
https://read.qxmd.com/read/38393535/molecular-cross-talk-between-long-covid-19-and-alzheimer-s-disease
#15
REVIEW
Magdalena Pszczołowska, Kamil Walczak, Weronika Misków, Katarzyna Antosz, Joanna Batko, Julia Karska, Jerzy Leszek
The long COVID (coronavirus disease), a multisystemic condition following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the widespread problems. Some of its symptoms affect the nervous system and resemble symptoms of Alzheimer's disease (AD)-a neurodegenerative condition caused by the accumulation of amyloid beta and hyperphosphorylation of tau proteins. Multiple studies have found dependence between these two conditions. Patients with Alzheimer's disease have a greater risk of SARS-CoV-2 infection due to increased levels of angiotensin-converting enzyme 2 (ACE2), and the infection itself promotes amyloid beta generation which enhances the risk of AD...
February 23, 2024: GeroScience
https://read.qxmd.com/read/38378084/accumulation-of-neutral-lipids-in-dystrophic-neurites-surrounding-amyloid-plaques-in-alzheimer-s-disease
#16
JOURNAL ARTICLE
Hao Huang, Md Golam Sharoar, Joseph Pathoulas, Liangliang Fan, Wanxia He, Rong Xiang, Riqiang Yan
Alzheimer's disease (AD) is characterized by the formation β-amyloid (Aβ) deposited neuritic plaques. Recent evidence suggests that abnormal lipid metabolism and accumulation could serve as biomarkers for neurodegenerative diseases, including AD. Tubular endoplasmic reticulum protein, reticulon 3 (RTN3), plays a crucial role in the development of neuritic plaque and lipid metabolism in AD brains. In present study, we sought to investigate a potential association between neutral lipid accumulation and AD pathology...
February 18, 2024: Biochimica et Biophysica Acta. Molecular Basis of Disease
https://read.qxmd.com/read/38365827/sodium-oligomannate-alters-gut-microbiota-reduces-cerebral-amyloidosis-and-reactive-microglia-in-a-sex-specific-manner
#17
JOURNAL ARTICLE
Megan E Bosch, Hemraj B Dodiya, Julia Michalkiewicz, Choonghee Lee, Shabana M Shaik, Ian Q Weigle, Can Zhang, Jack Osborn, Aishwarya Nambiar, Priyam Patel, Samira Parhizkar, Xiaoqiong Zhang, Marie L Laury, Prasenjit Mondal, Ashley Gomm, Matthew John Schipma, Dania Mallah, Oleg Butovsky, Eugene B Chang, Rudolph E Tanzi, Jack A Gilbert, David M Holtzman, Sangram S Sisodia
It has recently become well-established that there is a connection between Alzheimer's disease pathology and gut microbiome dysbiosis. We have previously demonstrated that antibiotic-mediated gut microbiota perturbations lead to attenuation of Aβ deposition, phosphorylated tau accumulation, and disease-associated glial cell phenotypes in a sex-dependent manner. In this regard, we were intrigued by the finding that a marine-derived oligosaccharide, GV-971, was reported to alter gut microbiota and reduce Aβ amyloidosis in the 5XFAD mouse model that were treated at a point when Aβ burden was near plateau levels...
February 17, 2024: Molecular Neurodegeneration
https://read.qxmd.com/read/38356322/microglial-reactivity-correlates-with-presynaptic-loss-independent-of-%C3%AE-amyloid-and-tau
#18
JOURNAL ARTICLE
Guoyu Lan, Xuhui Chen, Jie Yang, Pan Sun, Yue Cai, Anqi Li, Yalin Zhu, Zhen Liu, Shaohua Ma, Tengfei Guo
OBJECTIVE: Triggering receptor expressed on myeloid cells-2 (TREM2) and progranulin (PGRN) are critical regulators of microglia activation and can be detected in cerebrospinal fluid (CSF). However, whether microglial reactivity is detrimental or neuroprotective for Alzheimer disease (AD) is still debatable. METHODS: We identified 663 participants with baseline β-amyloid (Aβ) positron emission tomography (PET) and CSF biomarker data, including phosphorylated tau181 (p-Tau181 ), soluble TREM2 (sTREM2), PGRN, and growth-associated protein-43 (GAP-43)...
February 14, 2024: Annals of Neurology
https://read.qxmd.com/read/38352237/treatment-with-glatiramer-acetate-in-appswe-ps1de9-mice-at-an-early-stage-of-alzheimer-s-disease-prior-to-amyloid-beta-deposition-delays-the-disease-s-pathological-development-and-ameliorates-cognitive-decline
#19
JOURNAL ARTICLE
Zengyong Huang, Zhuo Gong, Yongtai Lin, Fan Yang, Weiping Chen, Shaotong Xiang, Yuedong Huang, Hao Xiao, Shuwen Xu, Jinhai Duan
BACKGROUND: Alzheimer's disease (AD) is characterized by neuroinflammation, which is frequently accompanied by immune system dysfunction. Although the mechanism of neurodegenerative lesions is unclear, various clinical trials have highlighted that early intervention in AD is crucial to the success of treatment. In order to explore the potential of immunotherapy in the early period of AD, the present study evaluated whether application of glatiramer acetate (GA), an immunomodulatory agent approved for remitting-relapsing multiple sclerosis (RRMS), in the early stages of AD prior to amyloid beta (Aβ) deposition altered the Aβ pathology and cognitive impairments in APPswe/PSEN1dE9 (APP/PS1) transgenic mice...
2024: Frontiers in Aging Neuroscience
https://read.qxmd.com/read/38317196/altered-amyloid-%C3%AE-structure-markedly-reduces-gliosis-in-the-brain-of-mice-harboring-the-uppsala-app-deletion
#20
JOURNAL ARTICLE
María Pagnon de la Vega, Stina Syvänen, Vilmantas Giedraitis, Monique Hooley, Evangelos Konstantinidis, Silvio R Meier, Johanna Rokka, Jonas Eriksson, Ximena Aguilar, Tara L Spires-Jones, Lars Lannfelt, Lars N G Nilsson, Anna Erlandsson, Greta Hultqvist, Martin Ingelsson, Dag Sehlin
Deposition of amyloid beta (Aβ) into plaques is a major hallmark of Alzheimer's disease (AD). Different amyloid precursor protein (APP) mutations cause early-onset AD by altering the production or aggregation properties of Aβ. We recently identified the Uppsala APP mutation (APPUpp), which causes Aβ pathology by a triple mechanism: increased β-secretase and altered α-secretase APP cleavage, leading to increased formation of a unique Aβ conformer that rapidly aggregates and deposits in the brain...
February 5, 2024: Acta Neuropathologica Communications
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