by Keyword: alpha-synuclein
Sala-Jarque, Julia, Gil, Vanessa, Andres-Benito, Pol, Martinez-Soria, Ines, Picon-Pages, Pol, Hernandez, Felix, Avila, Jesus, Luis Lanciego, Jose, Nuvolone, Mario, Aguzzi, Adriano, Gavin, Rosalina, Ferrer, Isidro, Antonio del Rio, Jose, (2024). The cellular prion protein does not affect tau seeding and spreading of sarkosyl-insoluble fractions from Alzheimer's disease Scientific Reports 14, 21622 
The cellular prion protein (PrPC) plays many roles in the developing and adult brain. In addition, PrPC binds to several amyloids in oligomeric and prefibrillar forms and may act as a putative receptor of abnormal misfolded protein species. The role of PrPC in tau seeding and spreading is not known. In the present study, we have inoculated well-characterized sarkosyl-insoluble fractions of sporadic Alzheimer's disease (sAD) into the brain of adult wild-type mice (Prnp(+/+)), Prnp(0/0) (ZH3 strain) mice, and mice over-expressing the secreted form of PrPC lacking their GPI anchor (Tg44 strain). Phospho-tau (ptau) seeding and spreading involving neurons and oligodendrocytes were observed three and six months after inoculation. 3Rtau and 4Rtau deposits from the host tau, as revealed by inoculating Mapt(0/0) mice and by using specific anti-mouse and anti-human tau antibodies suggest modulation of exon 10 splicing of the host mouse Mapt gene elicited by exogenous sAD-tau. However, no tau seeding and spreading differences were observed among Prnp genotypes. Our results show that PrPC does not affect tau seeding and spreading in vivo.
JTD Keywords: Alpha-synuclein, Alzheimer's disease, Amyloid-beta oligomers, Expression, Impairmen, Mapt, Mice, Paired helical filaments, Pathological tau, Prnp, Propagation, Prpc, Seeding, Spreadin, Synaptic plasticity, Tau, Tauopathies
Colom-Cadena, M, Davies, C, Sirisi, S, Lee, JE, Simzer, EM, Tzioras, M, Querol-Vilaseca, M, Sánchez-Aced, E, Chang, YY, Holt, K, McGeachan, RI, Rose, J, Tulloch, J, Wilkins, L, Smith, C, Andrian, T, Belbin, O, Pujals, S, Horrocks, MH, Lleó, A, Spires-Jones, TL, (2023). Synaptic oligomeric tau in Alzheimer's disease - A potential culprit in the spread of tau pathology through the brain Neuron 111, 2170-+
In Alzheimer's disease, fibrillar tau pathology accumulates and spreads through the brain and synapses are lost. Evidence from mouse models indicates that tau spreads trans-synaptically from pre- to postsynapses and that oligomeric tau is synaptotoxic, but data on synaptic tau in human brain are scarce. Here we used sub-diffraction-limit microscopy to study synaptic tau accumulation in postmortem temporal and occipital cortices of human Alzheimer's and control donors. Oligomeric tau is present in pre- and postsynaptic terminals, even in areas without abundant fibrillar tau deposition. Furthermore, there is a higher proportion of oligomeric tau compared with phosphorylated or misfolded tau found at synaptic terminals. These data suggest that accumulation of oligomeric tau in synapses is an early event in pathogenesis and that tau pathology may progress through the brain via trans-synaptic spread in human disease. Thus, specifically reducing oligomeric tau at synapses may be a promising therapeutic strategy for Alzheimer's disease.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
JTD Keywords: accumulation, alpha-synuclein, array tomography, cognitive impairment, dendritic spines, mouse model, neurodegeneration, neurons, synapses, Alzheimer, Amyloid-beta, Synapse, Tau
