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Dancing in the dark?

The status of late-onset Alzheimer’s disease genetics

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Abstract

Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder. Recent estimates suggest that possibly over 70% of the genetic variance for the disease remains unaccounted for by apolipoprotein E (APOE) and the three known early-onset AD genes (APP, PSEN1, PSEN2). Specifically, one recent segregation analysis predicted the existence of up to four additional susceptibility genes having a similar or greater effect than APOE. However, most of the nearly three dozen putative AD loci proposed to date have only been inconsistently replicated in follow up analyses and more studies are necessary to distinguish false-positive findings from genuine signals. Novel AD genes will not only provide valuable clues for the development of novel therapeutic approaches, but will also allow the development of new genetic risk-rofiling strategies that are an essential prerequisite for early prediction/prevention of this devastating disease. In this review, we will present a brief overview of analytic tools in complex disease genetics, as well as a summary of recent linkage and association findings indicating the existence of novel late-onset AD genes on chromosomes 12, 10, and 9.

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  1. Genetics and Aging Research Unit, Department of Neurology and Center for Aging, Genetics and Neurodegeneration, Massachusetts General Hospital Harvard Medical School, 114 16th Street, 02129, Charlestown, MA

    Lars Bertram & Rudolph E. Tanzi

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  1. Lars Bertram
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Correspondence to Rudolph E. Tanzi.

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Bertram, L., Tanzi, R.E. Dancing in the dark?. J Mol Neurosci 17, 127–136 (2001). https://doi.org/10.1385/JMN:17:2:127

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