Macroautophagy/autophagy deficit induces intracellular MAPT/tau accumulation, the hallmark pathology in Alzheimer disease (AD) and other tauopathies; however, the reverse role of MAPT accumulation in autophagy and neurodegeneration is not clear.
So far, AD cure remains elusive, but considering that AD progresses throughout tau pathology, which turns tau protein an appropriate target, besides tau is also included in other neurodegenerative disorders named as tauopathies.
Overall, our genetically matched mice have revealed that 4R NM hTau over expression is pathogenic in a manner distinct from classical aging-related tauopathy, underlining the importance of assaying the effects of transgenic disease-related proteins at appropriate stages in life.<b>SIGNIFICANCE STATEMENT</b>Due to differences in creation of transgenic lines, the pathological properties the P301L mutation confers to the tau protein <i>in vivo</i> have remained elusive, perhaps contributing to the lack of disease-modifying therapies for tauopathies.
Pathogenic mutations in the tau gene (microtubule associated protein tau, MAPT) are linked to the onset of tauopathy, but the A152T variant is unique in acting as a risk factor for a range of disorders including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and dementia with Lewy bodies (DLB).
Imbalance of neuronal proteostasis associated with misfolding and aggregation of Tau protein is a common neurodegenerative feature in Alzheimer's disease (AD) and other Tauopathies.
Aggregation of the microtubule-associated protein, tau, can lead to neurofibrillary tangle formation in neurons and glia which is the hallmark of tauopathy.
Since in Alzheimer's disease and related tauopathies tau proteostasis is compromised, here we sought to understand the role of tau protein in neuronal circadian biology and related behavior.
A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions.
Human tauopathies are neurodegenerative diseases with accumulation of abnormally phosphorylated and aggregated tau proteins forming neurofibrillary tangles.
Self-assembly of the microtubule-associated protein tau into neurotoxic oligomers, fibrils, and paired helical filaments, and cell-to-cell spreading of these pathological tau species are critical processes underlying the pathogenesis of Alzheimer's disease and other tauopathies.
Accumulation of misfolded and aggregated forms of tau protein in the brain is a neuropathological hallmark of tauopathies, such as Alzheimer's disease and frontotemporal lobar degeneration.
Further, differences in the ability of tau and mutant tau proteins to support prion-like propagation in various model systems raise questions about the generalizability of this mechanism in various tauopathies.
In this study, we demonstrate for the first time that insoluble tau isolated from human AD brain induces full-blown neurofibrillary pathology in a sporadic rat model of tauopathy expressing non-mutated truncated tau protein.
Alzheimer's disease (AD) and other tauopathies are characterized by intracellular accumulation of microtubule-associated tau protein leading to neurodegeneration.
Accumulating evidence suggests that misfolded MAPT (microtubule associated protein tau), the main component of neurofibrillary tangles in tauopathies, is subject to degradation by the autophagy-lysosomal pathway.
Hyperphosphorylation of the microtubule-associated protein tau and its resultant aggregation into neurofibrillary tangles (NFT) is a pathological characteristic of neurodegenerative disorders known as tauopathies.