Human postmortem tissue: what quality markers matter?
Postmortem human brain tissue is used for the study of many different brain diseases. A key factor in conducting postmortem research is the quality of the tissue. Unlike animal tissue, whose condition at death can be controlled and influenced, human tissue can only be collected naturalistically. This introduces potential confounds, based both on pre- and postmortem conditions, that may influence the quality of tissue and its ability to yield accurate results. The traditionally recognized confounds that reduce tissue quality are agonal factors (e.g., coma, hypoxia, hyperpyrexia at the time of death), and long postmortem interval (PMI). We measured tissue quality parameters in over 100 postmortem cases collected from different sources and correlated them with RNA quality (as indicated by the RNA Integrity Number (RIN)) and with protein quality (as measured by the level of representative proteins). Our results show that the most sensible indicator of tissue quality is RIN and that there is a good correlation between RIN and the pH. No correlation developed between protein levels and the aforementioned factors. Moreover, even when RNA was degraded, the protein levels remained stable. However, these correlations did not prove true under all circumstances (e.g., thawed tissue, surgical tissue), that yielded unexpected quality indicators. These data also suggest that cases whose source was a Medical Examiner's office represent high tissue quality.
Stan
Ana D
AD
University of Texas Southwestern Medical Center at Dallas, Department of Psychiatry, 5323 Harry Hines Blvd., NE5.110F, Dallas, TX 75390-9127, USA.
Ghose
Subroto
S
Gao
Xue-Min
XM
Roberts
Rosalinda C
RC
Lewis-Amezcua
Kelly
K
Hatanpaa
Kimmo J
KJ
Tamminga
Carol A
CA
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001344:Autopsy / Q000592:standards; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011180:Postmortem Changes; D011786:Quality Control; D012313:RNA / Q000032:analysis / Q000378:metabolism*; D020871:RNA Stability; D013048:Specimen Handling / Q000592:standards*; D013997:Time Factors
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D012313:RNA