Should persons with autosomal dominant AD be included in clinical trials 英文参考文献.docVIP

Grill and Ringman Alzheimer’s Research Therapy 2011, 3:18 /content/3/3/18 LETTER Should persons with autosomal dominant AD be included in clinical trials? Joshua D Grill* and John M Ringman ? ? See related review by Szigeti and Doody, /content/3/1/4, and related letter by Szigeti and Doody, /content/3/3/19 In a recent issue of Alzheimer’s Research erapy, we of Aβ deposits [2]. Biological di? er ences between ADAD read with great interest the discussion by Szigeti and and SAD might manifest similar di? erences in response Doody [1] of including early-onset Alzheimer’s disease or side-e? ect pro? le to a given intervention and thus (EOAD) (under age 65) in clinical trials. Successful should be considered care fully before patients with enroll ment is a challenge in most Alzheimer’s disease (AD) trials, and permitting the participation of these ADAD are enrolled in trials. In phase I studies, biological di? erences between young motivated patients could aid recruitment. EOAD ADAD and SAD could translate to di? erent dose require- can be categorized as AD caused by autosomal dominant mutations (ADAD) in the amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes and as AD in individuals not known or suspected ments since younger patients with ADAD are likely to have a more rapid drug metabolism. Females may also be premenopausal, making teratogenicity a consideration. In phase II, di? erences in ADAD could have e? ects on to harbor such mutations, which we here refer to as outcomes and interpretation since ADAD participants sporadic AD (SAD). might be overrepresented, given that the percentage of SAD patients who qualify for trials is low, ADAD patients have fewer barriers to participation, and trials