Alzheimer’s disease (AD) is a progressive neurodegenerative dis-order and the predominant form of dementia. Since its initial de-scription by Alois Alzheimer in 1906, several advances have been made in our understanding of the progression of the disease and its clinical consequences, yet the underlying etiology remains conten-tious. Given the stereotyped patts of cortical and hippocampal neuronal loss and the progressive degeneration of key neurotrans-mitter pathways, research has traditionally been focused on factors affecting neuronal viability, including the contribution of glial dysfunction to neuronal degeneration. From a clinical perspective, the fruits of this work have been underwhelming. Key pathological markers of the disease, including β-amyloid (Aβ) plaque formation and tau hyperphosphorylation, have yielded no effective therapies, highlighted by the recent discontinuations of several high profile Aβ immunotherapy trials. The few current symptomatic therapies for AD are predicated on the amelioration of cholinergic or gluta-matergic dysfunction. Aside from underscoring the inadequacy of current therapeutic approaches, this also points to the importance of altative contributors to AD pathogenesis. In recent years, there has been a growing appreciation for the multimodal and mul-tifactorial nature of the condition; the case for combinatorial thera-pies is thus strong.