Characterization of messenger RNA from the cerebral cortex of control and Alzheimer-afflicted brain.

Author(s): Guillemette JG, Wong L, Crapper McLachlan DR, Lewis PN

Publication: J Neurochem, 1986, Vol. 47, Page 987-97

PubMed ID: 2426413 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to determine if Alzheimer's disease alters RNA adenylation rates, RNase activity, transcript size distribution, or tail length.

   Summary of Findings:

   Although two different methods of RNA isolation provided differing total RNA yields, in both cases no significant difference in total RNA was observed between patients with Alzheimer's disease and those with no neurological diagnosis using either method. RNA yield was also independent of patient age (50-87 y) and postmortem interval (3-24 h). Poly(A) RNA yield was significantly lower as a percentage of total RNA in the patients with Alzheimer's disease (0.76%) when compared with the control group (1.3%), but no corresponding change in the unpolyadenylated fraction was observed. RNase activity tended to be higher in the Alzheimer's disease patients (20 +/-15 units/mg) than in control (12 +/-16 units/mg) but the difference was not significant (p>0.15) and thus is not likely to account for the decrease in poly(A) RNA. Densitometric analysis of northern blots showed that the distribution of poly(A) RNA did not appear to be different in Alzheimer's disease patients than in controls indicating differential degradation is also unlikely. Additionally, the length of the poly(A) tails was also unchanged between Alzheimer's disease and control groups so differences observed in total poly(A) are not due to differential column binding affinity. The authors conclude that in Alzheimer's disease there is a specific loss of poly(A) RNA that is not attributable to differences in RNAse activity, degradation or tail length.

   Biospecimens

   • Tissue - Brain

   Preservative Types

   • Frozen

   Diagnoses:

   • Alzheimer's Disease
   • Autopsy
   • Normal

   Platform:

   Analyte	Technology Platform
   RNA	Spectrophotometry
   RNA	Northern blot
   Protein	Enzyme assay
   RNA	Radioassay
   RNA	Colorimetric assay

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Diagnosis/ patient condition	Alzheimer's disease Control

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2. Study Purpose

   The purpose of this study was to determine if Alzheimer's or Huntington's disease alters in vitro translation capability of mRNA.

   Summary of Findings:

   Incorporation of sulfur 35 labeled methionine by in vitro translation using poly(A) mRNA from Alzheimer's disease patients yielded 1.76 times more protein per ug poly(A) RNA than controls (p<0.01). However when the protein produced from equivalent amounts of poly(A) mRNA was electrophoresed on 1 and 2 dimensional gels contrary to expectations less protein was apparent in the Alzheimer's disease samples. The authors attribute this to the Alzheimer's disease patients having less soluble protein and consequently a lot more insoluble protein. Electrophoresis of protein from Huntington's disease patients did not identify a similar change indicating this is specific to Alzheimer's disease. The authors conclude that mRNA from patients with Alzheimer's disease has higher in vitro translation capability but less protein that can be visualized in the author's system perhaps due to production of increased insoluble protein.

   Biospecimens

   • Tissue - Brain

   Preservative Types

   • Frozen

   Diagnoses:

   • Alzheimer's Disease
   • Huntington's Disease
   • Normal
   • Autopsy

   Platform:

   Analyte	Technology Platform
   RNA	In vitro translation
   Protein	1D/2D gels

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Diagnosis/ patient condition	Huntington's disease Alzheimer's disease Neurologically normal

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3. Study Purpose

   The purpose of this study was to determine the effect of fever and patient diagnosis (Alzheimer's disease, Huntington's disease, and normal) on the expression of heat shock protein by 2 dimensional gel analysis.

   Summary of Findings:

   Fever was associated with an increase in a 70 kDa protein which two dimensional analysis revealed was actually several proteins. Based on size it was hypothesized that these were heat shock proteins. Using a specific probe for heat HSP70 in northern blot analysis it was found that HSP70 increases with fever. HSP70 was also found to be lower in Alzheimer's disease, but not Huntington's disease patients after fever. The authors conclude that fever increases HSP-70, but the increase is partially attenuated in Alzheimer's disease patients and consequently final stage condition as well as diagnosis must be considered when comparing postmortem specimens.

   Biospecimens

   • Tissue - Brain

   Preservative Types

   • Frozen

   Diagnoses:

   • Autopsy
   • Alzheimer's Disease
   • Huntington's Disease
   • Normal

   Platform:

   Analyte	Technology Platform
   RNA	Northern blot
   Protein	1D/2D gels

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Preaquisition	Diagnosis/ patient condition	Alzheimer's disease Huntington's disease Neurologically normal
   Preaquisition	Prior patient medical condition	Degree of fever

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