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@ARTICLE{Davies:259960,
author = {Davies, Caitlin and Tulloch, Jane and Yip, Ellie and
Currie, Lydia and Colom-Cadena, Marti and Wegmann, Susanne
and Hyman, Bradley T and Wilkins, Lewis and Hooley, Monique
and Tzioras, Makis and Spires-Jones, Tara L},
title = {{A}polipoprotein {E} isoform does not influence
trans-synaptic spread of tau pathology in a mouse model.},
journal = {Brain and neuroscience advances},
volume = {7},
issn = {2398-2128},
address = {Thousand Oaks, CA},
publisher = {Sage Publishing},
reportid = {DZNE-2023-00813},
pages = {23982128231191046},
year = {2023},
abstract = {A key hallmark of Alzheimer's disease (AD) is the
accumulation of hyperphosphorylated tau in neurofibrillary
tangles. This occurs alongside neuroinflammation and
neurodegeneration. Pathological tau propagates through the
AD brain in a defined manner, which correlates with neuron
and synapse loss and cognitive decline. One proposed
mechanism of tau spread is through synaptically connected
brain structures. Apolipoprotein E4 (APOE4) genotype is the
strongest genetic risk factor for late-onset AD and is
associated with increased tau burden. Whether the
apolipoprotein E (APOE) genotype influences
neurodegeneration via tau spread is currently unknown. Here,
we demonstrate that virally expressed human tau (with the
P301L mutation) injected into mouse entorhinal cortex at 5-6
months or 15-16 months of age spreads trans-synaptically to
the hippocampus by 14 weeks post-injection. Injections of
tau in mice expressing human APOE2, APOE3 or APOE4, as well
as APOE knock-outs, showed that tau can spread
trans-synaptically in all genotypes and that APOE genotype
and age do not affect the spread of tau. These data suggest
that APOE genotype is not directly linked to synaptic spread
of tau in our model, but other mechanisms involving non-cell
autonomous manners of tau spread are still possible.},
keywords = {Alzheimer (Other) / apolipoprotein E (Other) / array
tomography (Other) / synapse (Other) / tau (Other) /
tauopathy (Other)},
cin = {AG Wegmann},
ddc = {610},
cid = {I:(DE-2719)1810006},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37600228},
pmc = {pmc:PMC10433884},
doi = {10.1177/23982128231191046},
url = {https://pub.dzne.de/record/259960},
}