Tau Seeding Mouse Models with Patient Brain-Derived Aggregates.

Tauopathies are a heterogeneous class of neurodegenerative diseases characterized by intracellular inclusions of aggregated tau proteins. Tau aggregates in different tauopathies have distinct structural features and can be found in different cell types. Transgenic animal models overexpressing human tau have been used for over two decades in the research of tau pathology.

Bispecific Tau Antibodies with Additional Binding to C1q or Alpha-Synuclein.

Background: Alzheimer's disease (AD) and other tauopathies are neurodegenerative disorders characterized by cellular accumulation of aggregated tau protein. Tau pathology within these disorders is accompanied by chronic neuroinflammation, such as activation of the classical complement pathway by complement initiation factor C1q. Additionally, about half of the AD cases present with inclusions composed of aggregated alpha-synuclein called Lewy bodies.

Viral Delivery of Non-Mutated Human Truncated Tau to Neurons Recapitulates Key Features of Human Tauopathy in Wild-Type Mice.

Background: Neuronal accumulation of hyperphosphorylated and truncated tau aggregates is one of the major defining factors and key drivers of neurodegeneration in Alzheimer's disease and other tauopathies.

Objective: We developed an AAV-induced model of tauopathy mediated by human truncated tau protein without familial frontotemporal dementia-related mutations to study tau propagation and the functional consequences of tau pathology.

Methods: We performed targeted transductions of the hippocampus or entorhinal cortex in adult mice followed by histological analysis to study the progression of hippocampal tau pathology and tau spreading.

Propagation of Tau Pathology: Integrating Insights From Postmortem and In Vivo Studies.

Cellular accumulation of aggregated forms of the protein tau is a defining feature of so-called tauopathies such as Alzheimer's disease, progressive supranuclear palsy, and chronic traumatic encephalopathy. A growing body of literature suggests that conformational characteristics of tau filaments, along with regional vulnerability to tau pathology, account for the distinct histopathological morphologies, biochemical composition, and affected cell types seen across these disorders. In this review, we describe and discuss recent evidence from human postmortem and clinical biomarker studies addressing the differential vulnerability of brain areas to tau pathology, its cell-to-cell transmission, and characteristics of the different strains that tau aggregates can adopt.

Intersection of pathological tau and microglia at the synapse.

Tauopathies are a heterogenous class of diseases characterized by cellular accumulation of aggregated tau and include diseases such as Alzheimer's disease (AD), progressive supranuclear palsy and chronic traumatic encephalopathy. Tau pathology is strongly linked to neurodegeneration and clinical symptoms in tauopathy patients. Furthermore, synapse loss is an early pathological event in tauopathies and is the strongest correlate of cognitive decline.