The estimated annual cost of healthcare for individuals living with Alzheimer’s disease (AD) or other dementias is almost $300 billion. In addition to this financial burden, the number of adults aged 65 or older is projected to double and it is expected an estimated 10 million of these individuals will develop AD by 2050. Despite global efforts to understand and ultimately assess, diagnose, and treat Alzheimer’s disease (AD) more effectively, a consensus definition of AD still does not exist. In 2018, the National Institute of Aging – Alzheimer’s Association (NIA-AA) Research Framework recommended that we should shift the definition of AD from a syndrome (i.e., the cognitive/behavioral symptoms that individuals present with) to a purely biological construct, specifically the presence of βamyloid deposition, pathologic tau, and neurodegeneration (the “A/T/N” model). In this episode, we talk to Dr. Adam Brickman about the NIA-AA Research Framework biological definition of AD, the role of vascular contributions, assumptions about the amyloid hypothesis, and implications of not including the clinical syndrome in the diagnosis of AD.