However, seminal studies in the 1980s failed to detect evidence of APP amplification in sporadic Alzheimer's disease peripheral blood and whole brain (Podlisny et al., 1987; St George-Hyslop et al., 1987; Tanzi et al., 1987) despite strong linkage in familial AD, thus linkage between sporadic AD and APP remains unclear. Here, APP is linked to early-onset autosomal dominant Alzheimer disease.