Increased plasma homocysteinemia is considered a risk factor of dementia, including Alzheimer's disease (AD) and vascular dementia. However, the reason elevated plasma homocysteinemia increases the risk of dementia remains unknown. A pathological hallmark of AD is neurofibrillary tangles (NFTs) that consist of pathologically phosphorylated tau proteins. The effect of homocysteine (Hcy) on tau a...

It is well established that tau pathology propagates in a predictable manner in Alzheimer's disease (AD). Moreover, tau accumulates in the cerebrospinal fluid (CSF) of AD's patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it...

Levels of tau in cerebrospinal fluid (CSF) are elevated in Alzheimer's disease (AD) patients. It is believed this elevation is related to the tau pathology and neurodegeneration observed in AD, but not all tauopathies have increased CSF tau. There has been little pre-clinical work to investigate mechanisms of increased CSF tau due to the difficulty in collecting CSF samples from mice, the most ...

Tauopathies are defined by assembly of the microtubule associated protein tau into filamentous tangles and classified by the predominant tau isoform within these aggregates. The major isoforms are determined by alternative mRNA splicing of exon 10 generating tau with three (3R) or four (4R) approximately 32 amino acid imperfect repeats in the microtubule binding domain. In normal adult brains t...

Tau hyperphosphorylation can be considered as one of the hallmarks of Alzheimer's disease and other tauophaties. Besides its well-known role as a microtubule associated protein, Tau displays a key function as a protector of genomic integrity in stress situations. Phosphorylation has been proven to regulate multiple processes including nuclear translocation of Tau. In this contribution, we are a...

Propagation of tau pathology is linked with progressive neurodegeneration, but the mechanism underlying trans-synaptic spread of tau is unknown. We show that stimulation of neuronal activity, or AMPA receptor activation, induces tau release from healthy, mature cortical neurons. Notably, phosphorylation of extracellular tau appears reduced in comparison with intracellular tau. We also find that...

Alzheimer’s disease (AD) is characterized by progressive loss of neurons in selected brain regions, extracellular accumulations of amyloid , and intracellular fibrils containing hyperphosphorylated tau. Tau mutations in familial tauopathies confirmed a central role of tau pathology; however, the role of tau alteration and the sequence of tau-dependent neurodegeneration in AD remain elusive. Usi...

Aggregation of highly phosphorylated tau into aggregated forms such as filaments and neurofibrillary tangles is one of the defining pathological hallmarks of Alzheimer's disease and other tauopathies. Hence therapeutic strategies have focused on inhibition of tau phosphorylation or disruption of aggregation. However, animal models imply that tau-mediated dysfunction and toxicity do not require ...

OBJECTIVE To investigate whether chronic traumatic encephalopathy (CTE) and CTE with amyotrophic lateral sclerosis (CTE-ALS) exhibit features previously observed in other tauopathies of pathologic phosphorylation of microtubule-associated protein tau at Thr175 (pThr175 tau) and Thr231 (pThr231 tau), and glycogen synthase kinase-3β (GSK3β) activation, and whether these pathologic features are a ...

The major protein subunit of the paired helical filaments (PHF) of Alzheimer disease (AD) is the microtubule-associated protein tau. Tau is a family of phosphopolypeptides that are abnormally phosphorylated in PHF. In this study, a non-PHF pool of tau abnormally phosphorylated at Ser-199/202, and tau not phosphorylated at this site (AD P-tau and AD tau, respectively) were isolated from the 27,0...