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Introduction

This report summarizes discussions at the second workshop on Enabling Technologies for Alzheimer's Disease (AD), held in August 2002 in Bar Harbor, Maine. Participants included academic and industry scientists from both inside and outside the field of Alzheimer's disease research, foundation representatives, and a program officer from the National Institute on Aging. The goals were to identify major knowledge gaps that are limiting progress in AD diagnosis and therapy, and to generate and share ideas about how new technologies and strategies might help bridge those gaps.

The recommendations presented here emerged during the discussion and do not necessarily reflect an order of priority or the unanimous views of all participants.

Gene Discovery

One major impediment has been the slow pace at which genomic screens and subsequent association studies have identified new risk genes. Participants discussed several strategies to accelerate this process. One involved broadening association studies to include all genes under the strongest linkage peaks. Participants also expressed enthusiasm for developing a comprehensive systems-biology study-analogous to that used to identify critical gene clusters in hypertensive rats-to identify AD-related gene clusters and the relationships between them.

Recommendations:

1. Several dozen human diseases map to the chromosome 10 region. All the genes in this region should be analyzed with multivariate analysis to detect subtle interactions.

2. Brains of people with Mendelian diseases mapping to an AD linkage region should be examined for AD pathology.

3. Consider comprehensive systems biology study to find new risk genes for neurodegeneration, including AD, using biomarkers validated in the National Coordinating Center series.

4. Use yeast, fly, and worm to discover novel genes and potential targets in neurodegeneration-related pathways.

5. Develop screens to look for loss-of-function mutations (independent and upstream of AbPP/tau) in aging cohorts (of mouse mutants) assembled by three large neurology centers nationwide.

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