Topic: hyperphosphorylated Tau

Age-associated dementias are neuropathologically characterized by the identification of hallmark intracellular and extracellular deposition of proteins, i.e., hyperphosphorylated-tau, amyloid-β, and α-synuclein, or cerebrovascular lesions. The neuropathological assessment and staging of these pathologies allows for a diagnosis of a distinct disease, e.g., amyloid-β plaques and hyperphosphorylated tau pathology in Alzheimer's disease. Neuropathological assessment in large scale cohorts, such as the UK’s Brains for Dementia Research (BDR) programme, has made it increasingly clear that the ageing

Alzheimer Disease’s (AD) etiology is a hot topic in neuroscience. Cholinergic hypothesis was the earliest theory while amyloidogenic hypothesis is currently the most studied. Unfortunately, despite massive and prolonged efforts, triggering events responsible for AD genesis remain elusive. Here, we aim to elucidate the cellular and molecular mechanisms that induce AD by focusing on glutamatergic tripartite synapses in hippocampus. It is known that Aβ binds to α7 Acetylcholine nicotinic receptors (α7nAchRs) with high affinity, favoring synaptic plasticity at physiological picomolar concentration

Spontaneous neuronal activity (SNA) plays an important role in the maturation and refinement of neuronal connections. However, neurodegenerative diseases, like tauopathies, can significantly alter SNA. Changes in SNA after the expression of tau mutations have not yet been analysed at presymptomatic stages. Furthermore, the currently available models lack the necessary complexity of the human brain to fully understand the underlying mechanisms of tau pathology and its effects on SNA. To address this, we present a novel in vitro platform utilizing cortical organoids (COs), derived from hPSCs, to

Anti-IgLON5 is a rare neurological disorder characterized by brainstem dysfunction, abnormal movements, sleep alterations, autoantibodies against IgLON5, and neurodegeneration, sometimes with neuronal deposits of tau. IgLON5 is a neural cell adhesion molecule of unknown function. This study was aimed to determine the effects of loss of function of IgLON5 in a Knockout (IgLON5-KO) mouse model assessing brain morphology, social behavior, and symptoms.IgLON5-KO mouse was produced by CRISPR-Cas9 technology. Two-month-old IgLON5-KO and wild-type mice were subjected to a comprehensive battery of beh

Alzheimer’s disease (AD), which is characterized by extracellular accumulation of amyloid-beta peptide and intracellular aggregation of hyperphosphorylated tau, is the most common form of dementia. During AD pathogenesis, tau is abnormally phosphorylated and aggregating within neurons. As a result of continuous intraneuronal tau aggregation, neurofibrillary tangles are formed. The aim of our project is to determine, whether inhibiting tau protein aggregation with a novel anti-aggregative compound “RE01” improves survival, behavior and neuropathology in a tau-transgenic mouse model. RE01 is an

Alzheimer’s disease is the leading cause of dementia among aging population. Currently accepted treatments are focused on the symptoms while efforts are made to the develop therapies that target the major pathological hallmarks i.e., β-amyloid (Aβ) plaques and hyperphosphorylated Tau tangles. Evidence from epidemiology and neuroimaging studies suggest that Type 2 Diabetes (T2DM) and Alzheimer's disease (AD) have a shared pathogenesis. Moreover, insulin resistance has been shown to impact hyperphosphorylation and aggregation of Tau making this an important risk factor for the detection of early

A growing number of studies on mouse models of Alzheimer's disease (AD) and AD patients recently focused the attention on the neuroprotective effects of irisin, a myokine released by muscles upon exercise. Based on these findings, in the present study we aimed to investigate, in a large cohort of AD patients, the levels of irisin in the cerebrospinal fluid (CSF) and plasma, and their correlations with disease biomarkers. Biological samples were obtained from patients with Alzheimer's dementia (n=82), mild cognitive impairment (n=44) and subjective memory complaint (n=20) biologically character

Alzheimer's disease (AD) is a tauopathy characterized by memory loss and cognitive decline. Tau protein plays a crucial role in the assembly and stabilization of microtubules. In disease conditions, aggregates of misfolded and hyperphosphorylated tau protein leads to neurofibrillary tangles. AD associated neurodegenerative changes in the brain are accompanied by structural of the retina, such as, optic nerve degeneration and reduced thickness of retinal layers. Numerous studies have shown the presence of tau aggregates in both AD mouse models and postmortem samples of AD patients’ retina. The

Alzheimer’s disease (AD) and type 2 diabetes (T2D) share common features, including insulin resistance. Brain insulin resistance has been implicated as a key factor in the pathogenesis of AD. Recent studies have demonstrated that sodium–glucose cotransporter-2 inhibitor (SGLT2-i) and dipeptidyl peptidase-4 inhibitor (DPP4-i) improve insulin sensitivity and provide neuroprotection. However, the effects of these two inhibitors on the brain metabolism and insulin resistance remain uninvestigated.We developed a T2D–AD mouse model using a high-fat diet (HFD) for 19 weeks along with a single dose of

The glutamatergic receptor mGlu5, being a modulator of neurotransmission in regions such as the cortex and hippocampus, plays a crucial role in learning and memory processing. Numerous studies highlight the alteration, contribution, and potential therapeutic targeting of mGlu5 in Alzheimer disease (AD). AD is the first cause of dementia, resulting in significant cognitive deficits, including memory loss due to the accumulation of Aβ, hyperphosphorylated tau, and neurodegeneration. In patients, brain asymmetric alterations, as Aβdepositions more pronounced in the left side, are reported early i