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The article by Martins et al.1 in this issue of Neurology proposes a novel approach to study the rate of progression in Alzheimer disease (AD). Predicting the course of AD is important for counseling patients and caregivers and for planning studies of intervention. Accurate modeling of the course of AD may also provide insights into its pathophysiology.
The common APOE ε4 allele confers an increased risk in late-onset AD.2 APOE ε4 may be associated with beta-amyloid and tangle pathology.3 The less common APOE ε2 allele may reduce risk. The rate of progression after the onset of AD is not as clearly related to the APOE allele, but if the APOE allele is associated with progression of pathology, earlier disease onset should be associated with more rapid progression. The current inconsistent relationship between APOE allele and prognosis has been difficult to reconcile with its relationship to onset of disease.
Modeling the clinical course of AD relies on appropriate study designs: following a well-defined sample of patients; enrolling patients at the same stage of disease; and …
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