NIH, National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) NIH - National Institutes of Health National Cancer Institute DCTD - Division of Cancer Treatment and Diagnosis

Postmortem interval effect on RNA and gene expression in human brain tissue.

Author(s): Birdsill AC, Walker DG, Lue L, Sue LI, Beach TG

Publication: Cell Tissue Bank, 2011, Vol. 12, Page 311-8

PubMed ID: 20703815 PubMed Review Paper? No

Purpose of Paper

The purpose of this paper was to investigate potential correlations between postmortem interval (PMI) and the duration of frozen storage with RNA analytical endpoints such as RNA integrity number (RIN), yield, and transcript levels in a large sample set of brain biospecimens.

Conclusion of Paper

PMI, regardless of diagnosis was significantly and negatively correlated to RNA yield and RIN, although the strength of the correlations were weak. PMI was also significantly, negatively, and modestly correlated to levels of 4 transcripts in brains collected from subjects diagnosed with Alzheimer's disease.

Studies

  1. Study Purpose

    The purpose of this study was to determine if RNA yield and integrity are correlated to PMI in brain specimens collected at autopsy from individuals diagnosed with Alzheimer's disease, Parkinson's disease, cerebrovascular disease, neurodegenerative disease, or neurological normal controls. A total of 79 brain specimens were collected and frozen by placement of 0.75 cm thick segments on dry ice, after which they were stored at -70 or -80 degrees C for 1-17 y before analysis.

    Summary of Findings:

    PMI was weakly, albeit significantly, negatively correlated to both RIN (r= -0.34; p=0.002) and RNA yield (r=-0.25; p=0.02). RIN and RNA yield were not significantly correlated with the subject's age, gender, diagnosis, or the length of time frozen specimens were stored prior to extraction and analysis.

    Biospecimens
    Preservative Types
    • Frozen
    Diagnoses:
    • Autopsy
    • Alzheimer's Disease
    • Parkinson's Disease
    • Normal
    • Other diagnoses
    Platform:
    AnalyteTechnology Platform
    RNA Automated electrophoresis/Bioanalyzer
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Preaquisition Postmortem interval 1-45 h (mean 6.6 h)
    Storage Storage duration 1-17 y
    Preaquisition Diagnosis/ patient condition Parkinson's disease
    Alzheimer's disease
    Cerebrovascular disease
    Neurodegenerative disease
    Neurologically normal
    Preaquisition Patient age 61-96 y (mean 81 y)
    Preaquisition Patient gender Female
    Male
  2. Study Purpose

    The purpose of this study was to determine if mRNA transcript levels are correlated to PMI in brain specimens collected at autopsy from individuals diagnosed with Alzheimer's disease. A total of 43 brain specimens were collected and frozen by placement of 0.75 cm thick segments on dry ice, after which they were stored at -70 or -80 degrees C before analysis for an unspecified length of time.

    Summary of Findings:

    Of the genes represented on the SABiosciences RT-Profiler PCR Array for Human Alzheimer's Disease, 4 transcripts (ADAM9, LPL, PRKCG, SERPINA3) displayed a significant and negative correlation to advancing PMI, although the strength of the correlations were modest (r= -0.419 to -0.468; p<0.01).

    Biospecimens
    Preservative Types
    • Frozen
    Diagnoses:
    • Autopsy
    • Alzheimer's Disease
    Platform:
    AnalyteTechnology Platform
    RNA Real-time qRT-PCR
    RNA Low density array
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Low density array Specific Targeted nucleic acid ADAM9
    LPL
    PRKCG
    SERPINA3
    Preaquisition Postmortem interval 1.5-45 h (mean 5.8 h)

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