Constellation of Risks and Processes Seen in Search for Alzheimer's Clues

THE SEARCH for the cause of Alzheimer's disease is sparking spirited debate. New ideas about the failure of apolipoproteins to bind to tau proteins, the main component of neurofibrillary tangles, are sharply criticized by most in the field, who have long placed blame on β amyloid, the main component of senile plaques. However, new evidence on many fronts suggests that there is probably not one single pathological route but rather several risk factors and pathological processes that, in various combinations, lead to the manifestations known as Alzheimer's disease (AD). Genes with roles in cancer as well as heart disease may be involved. So may sex hormones, growth factors, immune system responses, zinc, and apparently normal age-related changes, not alone but in concert with amyloid and tau. Many of these possibilities could offer therapeutic opportunities. For example, estrogen replacement therapy may reduce the risk of developing AD, and anti-inflammatory drugs might