TY - JOUR
T1 - Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes
AU - Delvaux, Elaine
AU - Bentley, Karen
AU - Stubbs, Victoria
AU - Sabbagh, Marwan
AU - Coleman, Paul D.
N1 - Funding Information:
This research was supported by NIH AGO-36400 (PC), NIH AG0-30429 (PC) and the State of Arizona and Arizona Department of Health Services , ADHS12-010553 (PC). The authors thank the brain bank and the Alzheimer's Disease Center at the University of Rochester for brain and clinical blood samples. From Banner Sun Health Research Institute, we also thank Dr Thomas Beach1, Lucia Sue, and their staff for tissue samples and postmortem evaluations, and the staff of Dr. Marwan Sabbagh for clinical blood samples.
Funding Information:
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 AG19610 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.
PY - 2013/6
Y1 - 2013/6
N2 - Because amyloid precursor protein (APP) fragments exist in many tissues throughout the body, including the fluid compartments of blood, they have been the focus of numerous investigations into their potential as a biomarker of Alzheimer's disease. Using immunohistochemistry, immunoelectron microscopy, Western blot, and quantitative real-time-polymerase chain reaction (qRT-PCR) analysis we examined whether APP processing in leukocytes is analogous to APP processing in the brain. We show APP immunoreactivity at light and electron microscopic levels in the cytoplasm and nucleus of peripheral blood leukocytes (PBL) yet our Western blot analysis data demonstrated that brain and PBL contain different APP fragments and differentially expressed APP processing enzymes. A Disintegrin and Metalloproteinase domain 10 (ADAM10), nicastrin, and beta-secretase 2 (BACE2) were present in brain but were undetected in PBL. Presenilin 1 and beta-secretase 1 (BACE1) were detected in both tissues but showed different patterns in Western blots. Quantitative PCR results identified Neprilysin as the only processing enzyme we interrogated in which Western and quantitative PCR data coincided. Although our data on differential processing of APP in brain and PBL point to exercising caution when generalizing between blood and brain with regard to mechanisms, they have no implications regarding utility as biomarkers.
AB - Because amyloid precursor protein (APP) fragments exist in many tissues throughout the body, including the fluid compartments of blood, they have been the focus of numerous investigations into their potential as a biomarker of Alzheimer's disease. Using immunohistochemistry, immunoelectron microscopy, Western blot, and quantitative real-time-polymerase chain reaction (qRT-PCR) analysis we examined whether APP processing in leukocytes is analogous to APP processing in the brain. We show APP immunoreactivity at light and electron microscopic levels in the cytoplasm and nucleus of peripheral blood leukocytes (PBL) yet our Western blot analysis data demonstrated that brain and PBL contain different APP fragments and differentially expressed APP processing enzymes. A Disintegrin and Metalloproteinase domain 10 (ADAM10), nicastrin, and beta-secretase 2 (BACE2) were present in brain but were undetected in PBL. Presenilin 1 and beta-secretase 1 (BACE1) were detected in both tissues but showed different patterns in Western blots. Quantitative PCR results identified Neprilysin as the only processing enzyme we interrogated in which Western and quantitative PCR data coincided. Although our data on differential processing of APP in brain and PBL point to exercising caution when generalizing between blood and brain with regard to mechanisms, they have no implications regarding utility as biomarkers.
KW - APP
KW - Alzheimer's disease
KW - Amyloid precursor protein
KW - Brain
KW - Differential processing
KW - Peripheral blood leukocytes
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U2 - 10.1016/j.neurobiolaging.2012.12.004
DO - 10.1016/j.neurobiolaging.2012.12.004
M3 - Article
C2 - 23298733
AN - SCOPUS:84875271668
SN - 0197-4580
VL - 34
SP - 1680
EP - 1686
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 6
ER -