@article{84025e6f05544ed384646f3c1763d7d7,
title = "Differential expression of tau species and the association with cognitive decline and synaptic loss in Alzheimer's disease",
abstract = "Pathological tau proteins in patients with Alzheimer's disease (AD) mainly accumulate in the form of neurofibrillary tangles (NFTs) and neuritic plaques (NPs). However, the molecular properties of tau species present in NFTs and NPs are not known. We tested the hypothesis that tau species within NFT-predominant tissue (NFT_AD) are distinct and more toxic than those in NP-predominant tissue (NP_AD). We analyzed the tau species from post mortem prefrontal cortical brains of NFT_AD and NP_AD. Compared to NP_AD, NFT_AD displayed highly phosphorylated tau oligomers, possessed tau oligomers in extracellular vesicles, and the 3-repeat (3R) and 4-repeat (4R) isoforms were differentially expressed between the groups. Comparison of tau proteins isolated from NFT- versus NP-AD subjects demonstrated higher tau seeding activity in NFT subjects and a greater degree of inducing synaptic loss in cultured neurons. We propose that tau species from NFT-predominant tissues possess greater levels of degenerative properties, thereby causing synaptic loss and cognitive decline.",
keywords = "Alzheimer's disease, cognitive impairment, extracellular vesicles and Serpina3n, neurodegeneration, synaptic loss, tau pathology",
author = "Saroja, {Sivaprakasam R.} and Abhijeet Sharma and Hof, {Patrick R.} and Pereira, {Ana C.}",
note = "Funding Information: We thank Mount Sinai Brain Bank (NIH NeuroBioBank) for providing human brain samples and the microscopy core facility at Icahn School of Medicine at Mount Sinai. This work was supported by funding from NIH R01 AG063819 (ACP), NIH R01AG064020 (ACP), NIH P50 AG005138 and P30 AG066514 (PRH), Paul B. Beeson Emerging Leaders Career Development Award in Aging K76 AG054772 (ACP), the BrightFocus Foundation (ACP), the DANA Foundation (ACP), the Alzheimer's Drug Discovery Foundation (ACP), the Alzheimer's Association (ACP), the Robert J. and Claire Pasarow Foundation (ACP), Carolyn and Eugene Mercy Research Fund (ACP), Karen Strauss Cook Research Scholar Award (ACP). We thank Radha Raghuraman for helping with data analysis. Funding Information: We thank Mount Sinai Brain Bank (NIH NeuroBioBank) for providing human brain samples and the microscopy core facility at Icahn School of Medicine at Mount Sinai. This work was supported by funding from NIH R01 AG063819 (ACP), NIH R01AG064020 (ACP), NIH P50 AG005138 and P30 AG066514 (PRH), Paul B. Beeson Emerging Leaders Career Development Award in Aging K76 AG054772 (ACP), the BrightFocus Foundation (ACP), the DANA Foundation (ACP), the Alzheimer's Drug Discovery Foundation (ACP), the Alzheimer's Association (ACP), the Robert J. and Claire Pasarow Foundation (ACP), Carolyn and Eugene Mercy Research Fund (ACP), Karen Strauss Cook Research Scholar Award (ACP). We thank Radha Raghuraman for helping with data analysis. Publisher Copyright: {\textcopyright} 2021 the Alzheimer's Association.",
year = "2022",
month = sep,
doi = "10.1002/alz.12518",
language = "English",
volume = "18",
pages = "1602--1615",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "John Wiley & Sons Inc.",
number = "9",
}