Measurement of Altered A beta PP Isoform Expression in Frontal Cortex of Patients with Alzheimer's Disease by Absolute Quantification Real-Time PCR Article

International Collaboration

cited authors

  • Tharp, William G., Lee, Yong-Ho, Greene, Shane M., Vincellete, Elise, Beach, Thomas G., Pratley, Richard E.

funding text

  • The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AGI9610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium) and the Michael J. Fox Foundation for Parkinson's Research.

abstract

  • Enzymatic cleavage of amyloid-beta protein precursor (A beta PP) produces amyloid-beta (A beta) peptides which form the insoluble cortical plaques characteristic of Alzheimer's disease (AD). A beta PP is post-transcriptionally processed into three major isoforms with differential cellular and tissue expression patterns. Changes in A beta PP isoform expression may be indicative of disease pathogenesis in AD, but accurately measuring A beta PP gene isoforms has been difficult to standardize, reproduce, and interpret. In light of this, we developed a set of isoform specific absolute quantification real time PCR standards that allow for quantification of transcript copy numbers for total A beta PP and all three major isoforms (A beta PP695, A beta PP751, and A beta PP770) in addition to glyceraldehyde-3-dehydrogenase (GAPDH) and examined expression patterns in superior frontal gyrus (SFG) and cerebellar samples from patients with (n = 12) and without AD (n = 10). Both total A beta PP and A beta PP695 transcripts were significantly decreased in SFG of patients with AD compared to control (p = 0.037 and p = 0.034, respectively). A beta PP751 and A beta PP770 transcripts numbers were not significantly different between AD and control (p > 0.15). There was trend for decreased percentage A beta PP695 (p = 0.051) and increased percentage A beta PP770 (p = 0.013) expression in SFG of patients with AD. GAPDH transcripts levels were also decreased significantly in the SFG of patients with AD compared to control (p = 0.005). Decreasing total A beta PP and A beta PP695 copy number was associated with increased plaque burden and decreased cognitive function. In this study we describe a simple procedure for measuring A beta PP isoform transcripts by real-time PCR and confirm previous studies showing altered A beta PP isoform expression patterns in AD.

authors

Publication Date

  • January 1, 2012

webpage

published in

category

start page

  • 449

end page

  • 457

volume

  • 29

issue

  • 2

WoS Citations

  • 8

WoS References

  • 30