His research has focused on the synaptic and endosomal pathology and biology of Alzheimer's disease. Beta-amyloid was traditionally viewed as an extracellular peptide that abnormally aggregates as amyloid plaques in the extracellular space with Alzheimer's disease. His publication Gouras GK et al., 2000, provided the first evidence that particularly the disease-linked Abeta42 variant initially accumulates within vulnerable neurons in human Alzheimer's disease, as well as in Down syndrome, a disorder that is also characterised by age-related amyloid pathology and dementia. Utilising immuno-electron microscopy his group subsequently discovered that Abeta42 localises to multivesicular bodies of normal neurons in the brain and with Alzheimer's disease, preferentially accumulates and aggregates in these late endosomes, particularly near synaptic terminals, providing the 1st physical link between beta-amyloid and synapses in the disease (Takahashi RH et al., 2002; 2004); as well as the 1st relation between beta-amyloid and early tau pathology within synaptic terminals (Takahashi RH et al., 2010).