Cytoskeletal messenger RNA stability in human neocortex: studies in normal aging and in Alzheimer's disease.

Author(s): Lukiw WJ, Wong L, McLachlan DR

Publication: Int J Neurosci, 1990, Vol. 55, Page 81-8

PubMed ID: 2084053 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to determine the effect of Alzheimer's disease on select transcripts.

   Summary of Findings:

   No change in PrP27-30, 18S ribosomal RNA or the 2600 bp transcript of H1 internucleosomal marker (HNF-L) were observed by northern blot in Alzheimer's disease. A specific reduction in the 4300 bp transcript of HNF-L was associated with Alzheimer's disease. The authors conclude that while no general effect of Alzheimer's disease on transcript abundance in the neocortex was observed there is a specific decline in the 4300 bp transcript of HNF-L.

   Biospecimens

   • Tissue - Brain

   Preservative Types

   • Frozen

   Diagnoses:

   • Alzheimer's Disease
   • Autopsy
   • Normal
   • Multiple Sclerosis

   Platform:

   Analyte	Technology Platform
   RNA	Dot blot or slot blot
   RNA	Northern blot

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Diagnosis/ patient condition	Alzheimer's disease Not Alzheimer's disease
   Northern blot Specific	Targeted nucleic acid	18S ribosomal RNA Human neurofilament light chain (HNF-L) Prion protein coding for the 27-30 kDa infectious particle (PrP27-30)

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2. Study Purpose

   The purpose of this study was to compare the effect of PMI on the decay of cytoskeletal specific RNAs in the neocortex by northern blot analysis.

   Summary of Findings:

   Postmortem degradation rates of the cytoskeletal mRNAs occurred in a transcript dependent manner. HNF-L, GFAP and alpha tubulin remained relatively stable until 4.5 h postmortem (86%, 87% and 92% of 0.7 h postmortem values respectively). The biggest decrease in stability for HNF-L, GFAP and alpha tubulin occurred between 4.5-6.5 h postmortem bringing levels down to 51%, 74%, and 78% of 0.7 h postmortem levels respectively. HNF-L, GFAP and alpha tubulin degradation continued reaching 36%, 60% and 72% of 0.7 h postmortem levels by 13.5 h postmortem respectively. In contrast, beta actin displayed the greatest magnitude of effect, degrading to 69% of 0.7 h postmortem values by 4.5 h and reaching 34% of 0.7 h postmortem values by 13.5 h postmortem. The authors postulate that postmortem RNA stability and size correlate loosely with long transcripts like HNF-L (4300 bp) being more stable than short transcripts such as beta actin (2000 bp). No effect of Alzheimer's disease on postmortem transcript stability was noted, but only HNF-L was compared directly. The authors conclude that PMI differentially affects the stability of RNA transcripts and that Alzheimer's disease does not have an overall affect on HNF-L postmortem transcript stability.

   Biospecimens

   • Tissue - Brain

   Preservative Types

   • Frozen

   Diagnoses:

   • Multiple Sclerosis
   • Pneumonia/Respiratory Infection
   • Cardiovascular Disease
   • Neoplastic - Carcinoma
   • Autopsy
   • Other diagnoses

   Platform:

   Analyte	Technology Platform
   RNA	Northern blot

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Postmortem interval	0.7 h 3.5 h 4.0 h 4.5 h 6.5 h 11.0 h 12.0 h 13.5 h
   Northern blot Specific	Targeted nucleic acid	Glial fibrillary acidic protein (GFAP) Human neurofilament light chain (HNF-L) Alpha tubulin Beta actin
   Preaquisition	Diagnosis/ patient condition	Alzheimer's disease Not Alzheimer's disease

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