Topic: amyloid plaques

Alzheimer's disease (AD) is a progressive neurological disorder characterized by amyloid accumulation and behavioral changes across preclinical and clinical stages. Although AD is currently incurable, emerging machine-learning (ML) approaches are facilitating novel insights into disease etiology and treatment mechanisms. Our study utilized and built upon two open-source ML platforms, DeepLabCut (Mathis et al. 2018) and Variational Animal Motion Encoding (VAME) (Luxem et al. 2022), to track and analyze naturalistic behavior in App knock-in (KI) and 5xFAD transgenic mouse models of AD. New human

Alzheimer's disease (AD) is one of the most significant neurodegenerative diseases, and its effective treatment remains a challenge. Dehydroepiandrosterone (DHEA) is an androgen molecule, which in vitro protects against amyloid-ß (Aß) toxicity, and so might potentially improve cognitive functions. As steroid might influence wide range of processes both short (via membrane receptors) and long term (via intracellular receptors) we can expect beneficial effect already after one injection.Six months old male 3xTg-AD mice were treated intraperitoneally with DHEAS (a water-soluble sulphate salt of D

Alzheimer's disease (AD) is a neurodegenerative disorder that is characterised by the gradual deterioration of executive functions and memory. Its primary pathophysiological hallmarks are amyloid plaques and neurofibrillary tangles. Promising humanised knock-in AD mouse models have been developed that exhibit Aβ pathology, neuroinflammation, synaptic dysfunction, and behavioural impairment. A rigorous battery of behavioural tests and analyses was utilised to further our knowledge of Alzheimer's disease.Our study comprised young (6-months), middle-aged (12-months), and old (22-months) AppNL-G-F

Histone deacetylase (HDAC) family proteins play important roles in pathological alterations of Alzheimer’s disease (AD). There has been keen interest in developing small molecule inhibitors of HDACs as potential therapeutics of AD. Presently, little is known about the role of HDAC11 in AD and whether HDAC11 can be a potential drug target for AD. Recently, we discovered PB94 as our lead small molecule inhibitor of HDAC11 exhibiting strong potency and selectivity against HDAC11 over other HDAC isoforms, which warranted further optimization and investigation for AD. Here, we optimized PB94 and an

Alzheimer’s disease, a neurodegenerative disorder characterized by progressive cognitive decline and accumulation of amyloid-plaques and neurofibrillary-tangles[1], begins with microstructural damage 10-20 years before cognitive symptoms appear[2]; developing novel non-invasive approaches to characterize early Alzheimer-specific patterns has great potential to improve diagnosis. Neuroinflammation accompanies plaque formation and is a potential target for early detection[2]. Here, we aimed to test advanced MRI-based inflammation biomarkers to capture microstructural differences between APP/PS1

Alzheimer’s disease (AD) is believed to have a prolonged preclinical phase when aggregates of soluble, neurotoxic tau and amyloid species accrue and slowly develop into positron emission tomography (PET)-detectable neurofibrillary tangles and amyloid plaques, respectively, which in turn herald the onset of mild cognitive impairment (MCI) and dementia. Hence, understanding the spatiotemporal timeline for the accrual of these early pathological species prior to PET detection and clinical symptoms will facilitate the development of disease-modifying AD therapies. In this study, we quantified the

A hallmark of Alzheimer’s disease (AD) pathology is amyloid plaques which can lead to neuroinflammation, cellular dysfunctions as well as altered neuronal activity. Both AD patients and mouse models exhibit abnormal neural oscillations, including altered gamma oscillations, hippocampal sharp wave-ripples (SWRs) and cortical sleep spindles. Although these oscillations play a role in memory formation and consolidation, it remains poorly understood how abnormal oscillations relate to novel experiences. Here we show that deficits in SWRs are experience-dependent in an AD mouse model. We performed

Identification of Alzheimer's disease (AD) risk loci highlighted the role of microglia in the pathogenies of AD. Nevertheless, whether microglia are beneficial or detrimental in AD is still debated. Several studies tested the contribution of microglia to amyloid pathology by microglia depletion, resulting in seemingly contradictory results. Here, we aimed to unify these conflicting findings by systematically testing microglia depletion at various stages of disease progression in mice.Depletion of microglia by PLX3397 treatment before the onset of amyloid plaques in AppNL-G-F mice resulted in a

Development of accurate biomarkers in the Alzheimer’s disease (AD) macaque model remains unattainable, in part because which aspects of macaque aging truly reflect comparable aspects of AD pathophysiology is unclear. To assess neuropathologic evidence underpinning biomarker development in macaques, we quantified ß-amyloid, pTau (AT8), neuroinflammatory marker and p16-expression in aging macaques (n=10) and AD patients (n=5). We assigned AD neuropathologic (ADNP) scores according to consensus guidelines. Further, we examined expression of pT217 and pT181 markers, acetylcholinesterase, tyrosine

Alzheimer’s disease (AD) is a complex disorder involving multiple genetic and non-genetic factors leading to cognitive decline and the accumulation of protein aggregates. Recently, we found that the epi-genetic regulation of Peptidase M20 Domain Containing 1 (PM20D1) modulates AD risk in humans and disease progression in mice through a still unknown mechanism. PM20D1 is an enzyme that facilitates the conjugation of N-acyl amino acids (NAAAs). However, whether NAAAs exert similar protective effects in AD remains unknown. To investigate this hypothesis, we NAAA-treated a series of AD models, and

To understand how amyloidosis in Alzheimer’s Disease changes circuit properties affecting memory encoding and recall, we examined the relationship between neuronal activity, nearness to amyloid plaques, and spatial memory readout from hippocampal CA1 place cells. We performed two-photon calcium imaging in head-fixed 5xFAD mice navigating an air-lifted circular track. Neuronal hyperactivity in CA1 during non-running periods was higher in 5xFAD mice compared to wildtype littermates in both young (2-3 months) and old (6.5-10 months) groups. Moreover, neurons close to amyloid plaques (<20µm in

Alzheimer’s disease (AD) presents a significant challenge to therapeutic interventions, necessitating the exploration of innovative strategies to manage its complex pathology. This study explores the relationship between autophagy and Transcription factor EB (TFEB) as a potential avenue for AD treatment. We demonstrate the therapeutic potential of TFEB in mitigating AD pathology by enhancing autophagy. Our strategy employs exosomes as vehicles for the targeted and efficient delivery of TFEB to affected cells. Exosomes, small extracellular vesicles, are recognized for their ability to cross bio

Dementia is a syndrome characterized by the progressive loss of cognitive functions, predominantly affecting older individuals. It is often accompanied by behavioral and psychological symptoms, significantly impacting dementia prognosis and treatment. Alzheimer's disease (AD) is the most common form of dementia, primarily affecting neurons in the cortex and hippocampus. The main pathological features of AD include extracellular accumulations of amyloid beta peptides in amyloid plaques and intracellular accumulations of hyperphosphorylated tau protein in neurofibrillary tangles. Since there is