Amyloid plaques appear to be the primary cause of Alzheimer’s disease, but what causes the buildup of beta-amyloid? Amyloid precursor protein (APP) is cleaved by two enzymes—beta-secretase and presenilin—to form extracellular beta-amyloid that builds up. Some neurons take up the beta-amyloid and then form neurofibrillary tangles in response. Another enzyme, apolipoprotein E (ApoE), breaks down beta-amyloid (Bu, 2009). Mutations in each of the genes that produce these proteins have been associated with Alzheimer’s disease, with presenilin mutations by far the most common (Bertram and Tanzi, 2008). Transgenic mice that produce extra beta-amyloid show progressive memory deficits as they age (Lesné et al., 2006).

This scenario, depicted in Figure 1, suggests several treatment strategies. One strategy is to inject antibodies that will bind beta-amyloid and slow the formation of plaques, but that approach does not seem to be effective (Holmes et al., 2008). Another strategy is to develop drugs that interfere with beta-secretase and/or presenilin activity (Singer et al., 2005), reducing beta-amyloid production. In the meantime, and in keeping with the repeated theme of this chapter—that genes and experience interact—there is good evidence that physical activity (LaFerla et al., 2007), mental activity (Willis et al., 2006), and adequate sleep (Kang et al., 2009) can postpone the appearance of Alzheimer’s disease.

Figure 1  The Beginning of the End


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