This paper demonstrates early changes in the structural white-matter connections that are disturbed in preclinical early-onset familial AD (eFAD). It is an outstanding example of a novel finding that demonstrates the power of using a small group of participants who are at known certain risk of AD with predictable age of onset.

Dr. Ringman should be congratulated on this exciting work. Studies of DTI in sporadic late-onset AD (LOAD) may compare similarities and differences between the two groups. For example, there are noted differences in the location of PET PIB deposition between eFAD and LOAD (see Klunk et al., 2007) that may explain some of the variations in clinical presentation (such as motor symptoms early in the course of some eFAD cases).

One might predict similar DTI findings in LOAD as are found in eFAD, given similar clinical findings of short-term memory disturbance.

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