Abstract Body

Alzheimer’s disease (AD) is a remarkably heterogenous disorder in terms of clinical and cognitive presentations, longitudinal trajectories and anatomic patterns of neurodegeneration. While most patients present with progressive memory loss, a significant minority show primary decline in language (i.e., logopenic variant of primary progressive aphasia), visuospatial/visuoperceptual abilities (posterior cortical atrophy), executive functions, behavior or sensorimotor integration. This talk will describe the neuroimaging correlates of heterogeneity in AD, evaluating in vivo the relationships between the burden and distribution of amyloid and tau, neurodegeneration, brain physiology and clinical features of the disease. We will present how data-driven approaches have revealed reproducible patterns of tau deposition and neurodegeneration in AD, each corresponding to unique patient characteristics and clinical profiles. We will review putative modulators of AD phenotypes, including age at symptom onset, sex, APOE (and other genetic factors), neurodevelopmental differences and comorbid neuropathologies. We will conclude by discussing ramifications of heterogeneity for drug development and future precision medicine approaches for treating AD.