ABSTRACT Breast cancer and Alzheimer's disease (AD) are common diseases of aging, and independently are responsible for significant morbidity and mortality in the United States. Recent clinical studies and large prospective population-based analyses have surprisingly suggested the presence of an inverse association between cancer and Alzheimer Disease (AD), one where cancer decreases the risk of development of dementia, and even AD. Other studies, however, have reported that breast cancer survivors demonstrate a significantly higher probability for AD, and implicated the ApoE e4 allele specifically in this interconnection. Therefore, the role of cancer in AD development remains highly controversial. Moreover, the mechanisms responsible for this interconnection remain largely unknown. It is the goal of this administrative supplement to R01CA194409, entitled “sEcad as a novel target and therapy for IGF-1R expressing tumors”, to investigate whether the development of breast cancer, with and without the benefit of our tumor-targeting anti-sEcad antibodies, have an impact on Alzheimer's disease in the novel APP/PS1;Neu compound transgenic mouse which develops both AD (APP/PS1 allele) and breast cancer (MMTV-Neu). To this end, we will temporally evaluate alterations in Aβ pathology, neuroinflammation and cognitive function in the APP/PS1;Neu double transgenic mouse model, which temporally compounds breast cancer and AD pathology. Heath Impact: The proposed administrative supplement will begin to address the very significant question of whether breast cancer has an impact on AD development, and enable the elucidation of mechanisms underlying such a putative interconnection. Completion of the proposed studies will provide the preliminary data necessary for future R01 grant applications. .