miR-17∼92 exerts stage-specific effects in adult V-SVZ neural stem cell lineages.

Neural stem cells (NSCs) in the adult ventricular-subventricular zone (V-SVZ) generate neurons and glia throughout life. MicroRNAs are important post-transcriptional regulators frequently acting in a context-dependent manner. Here, microRNA profiling defines cohorts of miRNAs in quiescent and activated NSCs, with miR-17∼92 highly upregulated in activated NSCs and transit amplifying cells (TACs) versus quiescent NSCs.

Proteomic Profiling of Extracellular Vesicles Separated from Plasma of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy.

Chronic Traumatic Encephalopathy (CTE) is a tauopathy that affects individuals with a history of exposure to repetitive head impacts, including National Football League (NFL) players. Extracellular vesicles (EVs) are known to carry tau in Alzheimer's disease and other tauopathies. We examined protein profiles of EVs separated from the plasma of former NFL players at risk for CTE.

Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues.

Introduction: Extracellular vesicles (EVs) from human Alzheimer's disease (AD) biospecimens contain amyloid beta (Aβ) peptide and tau. While AD EVs are known to affect brain disease pathobiology, their biochemical and molecular characterizations remain ill defined.

Methods: EVs were isolated from the cortical gray matter of 20 AD and 18 control brains.

Proteomic Profiling of Extracellular Vesicles Isolated From Cerebrospinal Fluid of Former National Football League Players at Risk for Chronic Traumatic Encephalopathy.

Chronic Traumatic Encephalopathy (CTE) is a tauopathy that affects individuals with a history of repetitive mild traumatic brain injury, such as American football players. Initial neuropathologic changes in CTE include perivascular deposition of phosphorylated microtubule-associated protein tau (p-tau) neurofibrillary tangles and other aggregates in neurons, astrocytes and cell processes in an irregular pattern often at the depths of the cortical sulci. In later stages, the p-tau depositions become widespread and is associated with neurodegeneration.

Tau Phosphorylation is Impacted by Rare AKAP9 Mutations Associated with Alzheimer Disease in African Americans.

We studied the effect of two rare mutations (rs144662445 and rs149979685) in the A-kinase anchoring protein 9 (AKAP9) gene, previously associated with Alzheimer disease (AD) in African Americans (AA), on post-translational modifications of AD-related pathogenic molecules, amyloid precursor protein (APP) and microtubule-associated protein Tau using lymphoblastoid cell lines (LCLs) from 11 AA subjects with at least one AKAP9 mutation and 17 AA subjects lacking these mutations. LCLs were transduced by viral vectors expressing causative AD mutations in APP or human full-length wild type Tau. Cell lysates were analyzed for total APP, Aβ, and total and T181 phospho-Tau (pTau).

Extracellular Vesicle Biology in Alzheimer's Disease and Related Tauopathy.

Extracellular vesicles (EVs) are physiological vesicles secreted from most eukaryotes and contain cargos of their cell of origin. EVs, and particularly a subset of EV known as exosomes, are emerging as key mediators of cell to cell communication and waste management for cells both during normal organismal function and in disease. In this review, we investigate the rapidly growing field of exosome biology, their biogenesis, cargo loading, and uptake by other cells.

Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche.

Adult neurogenic niches harbor quiescent neural stem cells; however, their in vivo identity has been elusive. Here, we prospectively isolate GFAP(+)CD133(+) (quiescent neural stem cells [qNSCs]) and GFAP(+)CD133(+)EGFR(+) (activated neural stem cells [aNSCs]) from the adult ventricular-subventricular zone. aNSCs are rapidly cycling, highly neurogenic in vivo, and enriched in colony-forming cells in vitro.