DOI: 10.1002/alz.075593 ISSN: 1552-5260

Amyloid beta and tau pathology compared within different Alzheimer’s disease mouse models after inoculation with Alzheimer’s disease brain tissue

Catherine Turnbull, Silvia Purro, John Collinge
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Alzheimer’s disease (AD), the leading cause of dementia worldwide, is associated with two proteins known as amyloid beta (Aβ) and tau. Both proteins are thought to have prion‐like properties, resulting in the seeded propagation and spread of disease‐related assemblies. We have investigated three different AD knock‐in mouse models containing humanised versions of Aβ and tau to further our understanding of how AD progresses after the inoculation of Aβ/tau assemblies or seeds. These transmissions would also aid in deciphering the prion‐like properties of both Aβ and tau. These included the APPNL‐F/NL‐F model, which contains a Swedish and Iberian mutation (NL‐F) in the amyloid precursor protein (APP), expressing elevated levels of human Aβ42, and the human (h)TauKI/KI model, which contains all six human isoforms of human tau. Moreover, the AppNL‐F/NL‐F/hTauKI/KI mouse model expresses both human tau and human Aβ42, allowing a side‐to‐side comparison of all three models to provide an informative insight into the best model to study Aβ and tau pathology after inoculation with AD cases.


We previously characterised three AD cases for prion‐like properties, in terms of protease resistance and conformational stability, and inoculated each of the cases into the different AD mouse models. Aβ and tau seeding was determined via histological and western blot analysis, via probing for 82E1 and AT8, to determine the presence of human Aβ and phosphorylated tau respectively.


Using transmission studies, significant differences were seen for Aβ and tau seeding within the APPNL‐F/NL‐F, human (h)TauKI/KI and AppNL‐F/NL‐F/hTauKI/KI mouse models. We show that the AppNL‐F/NL‐F/hTauKI/KI mouse model demonstrates both Aβ and tau seeding from the inoculation of AD cases at earlier time points compared to its retrospective APPNL‐F/NL‐F and hTauKI/KI mouse models in vivo.


After comparing the three different mouse models, our data suggests that the AppNL‐F/NL‐F/hTauKI/KI mouse model may be a superior model for studying prion‐like behaviour and the role of Aβ and tau assemblies within AD. With regards to future characterisation of possible Aβ and tau strains, we anticipate that this model will be able to distinguish any potential strains indicated from serial passages in vivo using the AppNL‐F/NL‐F/hTauKI/KI model.

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