Early Alzheimer's disease genetics

Article type: Research Article

Authors: Schellenberg, Gerard D.

Affiliations: E-mail: Zachdad@u.washington.edu

Abstract: The genetics community working on Alzheimer's disease and related dementias has made remarkable progress in the past 20 years. The cumulative efforts by multiple groups have lead to the identification of three autosomal dominant genes for early onset AD. These are the amyloid-β protein precursor gene (APP), and the genes encoding presenilin1 and 2. The knowledge derived from this work has firmly established Aβ as a critical disease molecule and lead to candidate drugs currently in treatment trials. Work on a related disease, frontotemporal dementia with parkinsonism – chromosome 17 type has also added to our understanding of pathogenesis by revealing that tau, the protein component of neurofibrillary tangles, is also a critical molecule in neurodegeneration. Lessons learned that still influence work on human genetics include the need to recognize and deal with genetic heterogeneity, a feature common to many genetic disorders. Genetic heterogeneity, if recognized, can be source of information. Another critical lesson is that clinical, molecular, and statistical scientists need to work closely on disease projects to succeed in solving the complex problems of common genetic disorders.

Keywords: Alzheimer disease, AβPP, genetics, mutation, tau

DOI: 10.3233/JAD-2006-9S341

Journal: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 367-372, 2006