It is noted that patients with Down syndrome show early onset Alzheimer’s disease; this could result from a combination of overexpression of APP, the precursor of the Aβ peptide and overexpression of SYNJ1, which results in decreased levels of PI(4,5)P2, altered cellular handling of the Aβ peptide and hence early onset disease. The gene discussed is SYNJ1; the disease is early-onset autosomal dominant Alzheimer disease.