TY  - JOUR
AU  - Davies, Caitlin
AU  - Tulloch, Jane
AU  - Yip, Ellie
AU  - Currie, Lydia
AU  - Colom-Cadena, Marti
AU  - Wegmann, Susanne
AU  - Hyman, Bradley T
AU  - Wilkins, Lewis
AU  - Hooley, Monique
AU  - Tzioras, Makis
AU  - Spires-Jones, Tara L
TI  - Apolipoprotein E isoform does not influence trans-synaptic spread of tau pathology in a mouse model.
JO  - Brain and neuroscience advances
VL  - 7
SN  - 2398-2128
CY  - Thousand Oaks, CA
PB  - Sage Publishing
M1  - DZNE-2023-00813
SP  - 23982128231191046
PY  - 2023
AB  - 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.
KW  - Alzheimer (Other)
KW  - apolipoprotein E (Other)
KW  - array tomography (Other)
KW  - synapse (Other)
KW  - tau (Other)
KW  - tauopathy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37600228
C2  - pmc:PMC10433884
DO  - DOI:10.1177/23982128231191046
UR  - https://pub.dzne.de/record/259960
ER  -