1. NIA LOAD Genetics Initiative Progress Report 2006: NCRAD and LOAD Update Michele Goodman, CCRP National Cell Repository for Alzheimer’s Disease

2. NCRAD Update Over 800 families currently enrolled Continue to recruit new families  2+ living with early or late onset AD, related dementia  Qualifying families should contact NCRAD 1-800-526-2839 or www.ncrad.orgwww.ncrad.org Good option for families who fail to meet LOAD criteria (not sibs, no 3rd person over age 60)

3. NCRAD Update: Recruitment Family referral from NCRAD to Sites:  2003: 131 Families  2004: 112 Families  2005: 28 Families  2006 so far: 11 Families Common recruitment sources  Internet, Alzheimer’s Association, clinicaltrials.gov, newspaper NCRAD/Columbia plan to attend several small regional conferences

4. NCRAD Update: Recruitment Call and e-mail volume at NCRAD  2003: 100+ calls, 40-50 e-mails per day ~10% from qualifying families  2006: 1-10 calls, 1-5 e-mails per day Much higher proportion of qualifying families Sites recruiting new families Sample collection numbers mirror recruitment trend

5. Samples Sent to NCRAD

6. NCRAD Update: Sample Requests Researchers now requesting samples from NCRAD and LOAD families  NCRAD pedigrees currently online at www.ncrad.org  LOAD pedigrees will be online soon Will highlight resources at 10 th Annual International Conference on Alzheimer’s Disease and Related Disorders in July  NCRAD booth in exhibit hall

7. NCRAD Update: Sample Requests 1,985 LOAD samples distributed to researchers  1,700 to outside investigators  285 to LOAD investigators 1,973 NCRAD samples distributed during same time

8. NCRAD Update: Sample Requests LOAD sample requests will increase  Standardized phenotypic data  Longitudinal data sets  Controls with MDS NCRAD samples still ordered for autopsy confirmed AD  360+ sampled CONF AD in NCRAD  80 sampled CONF AD in LOAD Only 10 families with 2 or more autopsies

9. LOAD Update: Site Notes Columbia  February trip to rural Kentucky 6 individuals evaluated + 2.5 hour drive + only one flight in/out of Lexington = quite a trip!  March trip to D.C. area for 8 family members, including FTD patient  March trip to Alabama  30 individuals evaluated  Interesting conversation between family members

10. LOAD Update: Site Notes Mayo Jacksonville  Will see large family in Alabama with many affected, interested in autopsy Mayo Rochester  Recent trip to Sarasota, FL Met with 7 individuals, 5 enrolled with more to participate later  Marshalltown, IA trip on 4/17/06 Sampled and evaluated 20 individuals in a family with 11 sibs  Just enrolled 8 th living of 17 sibs  3 new families scheduled in May

11. LOAD Update: Site Notes Indiana University  Recently evaluated 9 sibs in Dixon, IL (boyhood home of Ronald Reagan)  Completed several local visits, and hope to plan more Midwest trips  Family filmed for local TV news special  New brochure for control recruitment

12. LOAD Update: Site Notes University of Texas Southwestern (UTSW)  Enrolled/enrolling 11 families since April 2005  Traveled to various cities in Texas, Oklahoma, Louisiana  Will see families near Tulsa, Houston/Austin  Study visits educate and raise awareness in families Offspring traveling to UTSW for follow-up visits

13. LOAD Update: Site Notes University of Washington  Great Falls, Montana and surrounding area 9 evaluated in single family  Salem, Oregon 3 individuals from 2 families  Planned trip to central Washington  Another way to evaluate a family member…have them take your coat

14. LOAD Update: Site Notes Washington University  Trips during past 8 months for 8 families and 24+ individuals Southern/Northern California, Idaho, Northern Kentucky, Kansas, Louisiana, Texas  Upcoming trips to Texas, Florida, Kansas, Utah, New Mexico  Level of family commitment and contribution to Wash U. ADRC

15. LOAD Update The Good News  Data calls going well, less errors to report  Recently ascertained several large families with a few more in progress  February 2006 data call produced 20+ additional qualifying families Excellent Work!! And we also met our goal for CIDR…

16. CIDR Submitted 2,514 samples in December:  2,402 LOAD and Control samples 2,107 LOAD family samples 295 Control samples  112 investigator duplicates  Entire pedigree file recoded 362 LOAD families sent to CIDR  321 qualifying families  41 nearly qualifying families

17. CIDR: Error Report 54 Reported Errors (2%)  And 21 resulted from a CIDR plate automation problem, so really only 33 (1%) 3 Unique Situations (not actual errors)  1 verified Klinefelter syndrome (XXY)  Identical twin sisters married brothers in AD family 30 errors left to investigate

18. CIDR: Error Report 8 Performed poorly in SNP Assay  No particular reason cited by CIDR 8 Data Coding Errors  Incorrect gender coding or wrong parents 14 NCRAD/Lab Errors  DNA errors should be independent of cell lines

19. CIDR: Error Report Next steps:  Lab sends new aliquot of DNA for 22 problem samples  NCRAD submits new file to CIDR with corrected pedigree data NCRAD will continue 9 marker screen on new samples and DNA from cell lines  Clean, verified pedigree structure necessary for future rounds of genotyping

20. Pedigree Review Every 6 months following data call and data cleaning Each site asked to provide updated list of “completed” families  Both qualifying and dead end families NCRAD will plot completed families for each site from MDS Fax or mail to site for verification

21. Pedigree Review After site verifies family structure, samples will be screened in IU lab If errors reported: 1. NCRAD verifies that sample IDs correct 2. Reference data set and initial pedigree submitted by site 3. Contact site to validate data 4. Investigate sources of lab error

22. Pedigree Review Next pedigree review July 2006  Send list of completed families with data or dataclean files NCRAD will not release samples to investigators until pedigree review process is complete 362 CIDR families and 295 Controls currently available to researchers

23. NCRAD Lab 99% cell line success rate across all AD studies  Some failed cells sent again and growing well Creating DNA back-up  100 µl stored in separate facility Requests additional information for frozen brain specimens  Amount of tissue indicated on sample form

24. Summary Need to increase autopsy #’s in LOAD Pedigree review important to increase available samples  Anticipate new investigators after July conference and CIDR analysis Value of genotyping Hope to gain more qualifying families with follow-up