Skip to Content
MilliporeSigma
  • Humanized Tau Mice with Regionalized Amyloid Exhibit Behavioral Deficits but No Pathological Interaction.

Humanized Tau Mice with Regionalized Amyloid Exhibit Behavioral Deficits but No Pathological Interaction.

PloS one (2016-04-14)
Michael J Yetman, Stephanie W Fowler, Joanna L Jankowsky
ABSTRACT

Alzheimer's disease (AD) researchers have struggled for decades to draw a causal link between extracellular Aβ aggregation and intraneuronal accumulation of microtubule-associated protein tau. The amyloid cascade hypothesis posits that Aβ deposition promotes tau hyperphosphorylation, tangle formation, cell loss, vascular damage, and dementia. While the genetics of familial AD and the pathological staging of sporadic disease support this sequence of events, attempts to examine the molecular mechanism in transgenic animal models have largely relied on models of other inherited tauopathies as the basis for testing the interaction with Aβ. In an effort to more accurately model the relationship between Aβ and wild-type tau in AD, we intercrossed mice that overproduce human Aβ with a tau substitution model in which all 6 isoforms of the human protein are expressed in animals lacking murine tau. We selected an amyloid model in which pathology was biased towards the entorhinal region so that we could further examine whether the anticipated changes in tau phosphorylation occurred at the site of Aβ deposition or in synaptically connected regions. We found that Aβ and tau had independent effects on locomotion, learning, and memory, but found no behavioral evidence for an interaction between the two transgenes. Moreover, we saw no indication of amyloid-induced changes in the phosphorylation or aggregation of human tau either within the entorhinal area or elsewhere. These findings suggest that robust amyloid pathology within the medial temporal lobe has little effect on the metabolism of wild type human tau in this model.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
SIGMAFAST 3,3′-Diaminobenzidine tablets, tablet, To prepare 15 mL
Sigma-Aldrich
Anti-GAPDH Antibody, from chicken, purified by affinity chromatography