1. NCRAD Update Tatiana Foroud, Ph.D. Indiana University

2. Identify Appropriate Families Send Columbia a Preliminary Pedigree Obtain samples/complete study visits Transfer Minimal Datatset to NCRAD Send Columbia the Sampled Pedigree

3. Identify Appropriate Families

4. Appropriate Families for Study   At least 2 living siblings with LOAD (onset > 60 years)   At least 1 other living related family member who :   Has AD (onset > 50 years) Or   Is unaffected (> 60 years)

5. Who to collect?   Genetic analysis seeks to study the transmission of marker alleles throughout the family.   When we can determine the inheritance of all marker alleles unambiguously, we have the greatest power to find genes for disease!   Unaffected individuals may be very important for collection.

6. Which are the best families?   Families with the largest number of affected individuals.   Strong family history suggests more genetic effects.   Unaffected individuals in families with many affected individuals are also very important, particularly if they are examined clinically.

7. Who to Collect   Collect the parents in generation I, if available   Collect all siblings in generation II (affected and unaffected)   Collect any individuals in generation III with memory loss   Collect any individuals in generation III > 50 years   Query for any other affected cousins, half siblings, aunts, uncles?? I II III

8. Unaffected Individuals n n We focus the collection of unaffected individuals on those: – –Over the age of 50 years – –Willing to undergo a cognitive evaluation (telephone or in person) – –Siblings and offspring of affected individuals n n Some others very much want to participate – use judgment!

9. Preliminary Pedigree

10. The Preliminary Pedigree   Is sent to the Coordinating Center at Columbia and should include:   Diagnosis   Current age   Age at onset   Who will likely be sampled   It is highly recommended to include the family and individual number.

11. Data Collection

12. Study Visit/Data Collection n Based on recommendations from the Coordinating Center –Samples and study visits are collected from all targeted individuals who are willing to participate

13. Minimal Dataset

14.   A minimal dataset must be completed for all individuals from whom a biological sample has been sent to NCRAD   Includes deceased individuals when an autopsy specimen is being sent

15. Minimal Dataset   The minimal dataset is transferred each quarter to Indiana University. The contact person is:   Michael Daubs, Database Manager   email: mdaubs@iupui.edumdaubs@iupui.edu   tel: 317-278-2608

16. Sampled Pedigree

17. The Sampled Pedigree   Is sent to the Coordinating Center at Columbia and should include:   All individuals identified by their family and individual number.   Who was sampled.   Who had a minimal dataset collected.   Who had neuropsychological testing

18. Sampled Families   A family cannot be considered ‘completed’ or ‘sampled’ until the minimal dataset is transferred to NCRAD for all biologically sampled individuals   This is essential, since without the minimal dataset, we can determine whether the family meets the study criteria

19. Pedigree Sample Reports Fam IDInd ID Sample at NCRAD? Data Set at NCRAD? Need Data?Comments 60119Yes No 60120Yes No 60132YesNoYesNeed data 60133YesNoYesNeed data 60121NoYesNo 60122Yes No 60123NoYesNo

20. Pedigree Sample Reports Fam IDInd ID Sample at NCRAD? Data Set at NCRAD? Need Data?Comments: 5659NoYesNo 5657Yes No 56510NoYesNo 56526YesNoYes Have sample, not on pedigree, no data set on file.

21. Pedigree Sample Reports n n NCRAD sends out this report after receiving a copy of the sampled pedigree. n n This report highlights missing data that is required for a family to be considered sampled or complete. n n Important for sites to respond and submit missing information

22. Qualified Families Based on Submitted Data n n 205 families have a minimal dataset submitted to NCRAD for at least one family member n n Only 90 families consist of: – – At least 2 siblings with a minimal dataset supporting AD – – At least one other biologically related family member meeting the age requirements and with a minimal dataset

23. Qualified Families Based on Submitted Data n n In the majority of families who do not qualify, the problems are: – –A minimal dataset has not been submitted for the critical individuals – –Missing variables in the minimal dataset preclude the family from qualifying n n There are a small number of families who will never qualify. NCRAD and Columbia should be informed when the ‘sampled’ pedigree is submitted

24. Samples to Researchers n n Researchers can request LOAD samples – –At this time, with only limited MDS data, no requests have been processed – –MTA out would be required – –Requests for samples should include: n n IRB approval for proposed analyses n n Investigator CV n n Short description of proposed studies

25. Minimal Dataset and Sampled Pedigree n n These are both critical elements that the site must submit. n n Without both of these elements, NCRAD and Columbia can not determine if a family meets LOAD criteria. n n Without both of these elements, the family will not be as useful to researchers!