A Nelson-Aalen Estimate of the Incidence Rates of Early-Onset Alzheimer's Disease Associated with the Presenilin-1 Gene

We analyse, in a probabilistic setting, Newcombe's (1981) life table method of estimating rates of onset of high-penetrance single-gene disorders, and extend this to a counting process model for individual life histories, including movement between risk groups arising from genetic testing and onset in relatives. We derive Nelson-Aalen-type estimates of the integrated intensity of onset, including a useful diagnostic check on the treatment of censored observations. We summarise the literature on mutations in the Presenilin-1 (PSEN-1) gene, associated with early-onset Alzheimer's disease (EOAD), and use published pedigrees to estimate (approximately) the rate of onset of EOAD.

Keywords: Early-Onset Alzheimer's Disease; Nelson-Aalen Estimate; Presenilin-1 Gene; Pedigrees