We collected and analyzed genomic sequencing data from individuals with clinician-diagnosed early-onset or atypical dementia and, in many cases, their family members. One hundred total patients were described. Pathogenic variants, as well as established risk variants, were returned to patients. A polygenic risk score (PRS) was calculated for Alzheimer’s patients and compared to the scores of a late-onset Alzheimer’s cohort and a control set. Patients with early-onset Alzheimer’s had higher non-APOE PRSs than patients with late-onset Alzheimer’s, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk.