Diabetes mellitus (DM) is one of the most devastating diseases that currently affects
the aging population. Recent evidence indicates that DM is a risk factor for many
brain disorders, due to its direct effects on cognition. New findings have shown that
the microtubule‐associated protein tau is pathologically processed in DM; however,
it remains unknown whether pathological tau modifications play a central role in the
cognitive deficits associated with DM. To address this question, we used a gain‐of‐
function and loss‐of‐function approach to modulate tau levels in type 1 diabetes
(T1DM) and type 2 diabetes (T2DM) mouse models. Our study demonstrates that
tau differentially contributes to cognitive and synaptic deficits induced by DM. On
one hand, overexpressing wild‐type human tau further exacerbates cognitive and
synaptic impairments induced by T1DM, as human tau mice treated under T1DM
conditions show robust deficits in learning and memory processes. On the other
hand, neither a reduction nor increase in tau levels affects cognition in T2DM mice.
Together, these results shine new light onto the different molecular mechanisms
that underlie the cognitive and synaptic impairments associated with T1DM and
T2DM.
