In Alzheimer's disease (AD), the pathological accumulation of tau appears to be a downstream effect of amyloid β protein (Aβ). However, the relationship between these two proteins and memory loss is unclear. In this study, we evaluated the specific removal of pathological tau oligomers in aged Tg2576 mice by passive immunotherapy using tau oligomer-specific monoclonal antibody. Removal of tau o...

Tau is an intrinsically disordered protein with a central role in the pathology of a number of neurodegenerative diseases. Tau normally functions to stabilize neuronal microtubules, although the mechanism underlying this function is not well understood. Of note is that the interaction between tau and soluble tubulin, which has implications both in understanding tau function as well as its role ...

Frontotemporal dementia (FTD) and other tauopathies characterized by focal brain neurodegeneration and pathological accumulation of proteins are commonly associated with tau mutations. However, the mechanism of neuronal loss is not fully understood. To identify molecular events associated with tauopathy, we studied induced pluripotent stem cell (iPSC)-derived neurons from individuals carrying t...

One of the hallmarks of Alzheimer's disease is the formation of neurofibrillary tangles, intracellular aggregates of hyperphosphorylated, mislocalized tau protein, which are associated with neuronal loss. Changes in tau are known to impair cellular transport (including that of mitochondria) and are associated with cell death in cell culture and mouse models of tauopathy. Thus clearing pathologi...

The proteasomal degradation of cytosolic, phosphorylation-independent tau in human brains is potentially linked to the pathogenesis of neurofibrillary pathology in Alzheimer's disease (AD). Previous studies showed that the active 20S proteasome core degrades recombinant tau effectively, which prompted this study to determine if there was evidence of proteasomal degradation of tau in human brain...

Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-sp...

Filamentous tau inclusions in neurons and glia are neuropathological hallmarks of sporadic and familial tauopathies. Because tau gene mutations are pathogenic for the autosomal dominant tauopathy "frontotemporal dementia and parkinsonism linked to chromosome 17," tau abnormalities are implicated directly in the onset and/or progression of disease. Although filamentous tau aggregates are acknowl...

PURPOSE Increased immunoreactivity (IR) of beta-amyloid and the amyloid-associated proteins tau and amyloid precursor protein (APP) in the brain have been linked to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. However, the expression of these proteins has not been investigated in the normal or diseased human retina. METHODS Using immunohistochemical techniques,...

TAU is a microtubule-associated protein that under pathological conditions such as Alzheimer's disease (AD) forms insoluble, filamentous aggregates. When 20 years after TAU's discovery the first TAU transgenic mouse models were established, one declared goal that was achieved was the modeling of authentic TAU aggregate formation in the form of neurofibrillary tangles. However, as we review here...

Maximal amounts of tubulin in rat brain are observed during the 3 to 10-day postnatal period. The rates of in vitro tubulin polymerization are very low at these stages of development; they increase thereafter during the second postnatal week, reaching a maximum at adulthood. The increased rate of polymerization could depend either on modifications in the concentration and activity of microtubul...