Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes

Delvaux, Elaine; Bentley, Karen; Stubbs, Victoria; Sabbagh, Marwan; Coleman, Paul D.

doi:10.1016/j.neurobiolaging.2012.12.004

Cited by 26Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes

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Delvaux, Elaine, Bentley, Karen, Stubbs, Victoria, Sabbagh, Marwan, Coleman, Paul D.·2013·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2012.12.004PMC PMC3598628

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Abstract

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.

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APP is expressed and processed in T-cells at low levels.
“APP is expressed and processed in T-cells at low levels (26) – accumulation and processing of APP lead to mitophagic changes in neurons (27).”
From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [26]
The Results (§3.1) show APP immunoreactivity in peripheral blood leukocytes, and the Discussion (§4) describes evidence of APP processing in those cells. But the Discussion explicitly says the authors did not distinguish leukocyte subclasses, so the paper does not establish the claim specifically for T-cells or show that their APP levels are low. (LLM, conf=0.90)
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Authors: Delvaux, E., Bentley, K., Stubbs, V., Sabbagh, M., & Coleman, P. D.
Affiliations: Banner Sun Health Research Institute (US)
University of Rochester Medicine (US)
Corresponding author: Delvaux, Elaine
ORCID: Delvaux, Elaine
Bentley, Karen
Sabbagh, Marwan
Coleman, Paul D.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2013-06
Volume: 34
Issue: 6
Pages: 1680-1686
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2012.12.004
PMC: PMC3598628
OpenAlex: W2066472534
Cited by: 26
References: 40
Citations by year: 2026: 5 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1
FWCI: 0.93
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Arizona Department of Health Services (ADHS12-010553, 211002)
National Institute of Neurological Disorders and Stroke (U24 NS072026)
National Institute on Aging (P30 AG19610)
Arizona Biomedical Research Commission (4001, 0011, 05-901, and 1001)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: amyloid precursor protein, APP processing, peripheral blood leukocytes, brain, Alzheimer's disease biomarkers, ADAM10, nicastrin, BACE2, BACE1, presenilin 1, neprilysin
MeSH terms: Alzheimer Disease, Brain, Humans, Leukocytes, Mononuclear, Parkinson Disease, Biomarkers, Amyloid beta-Protein Precursor

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Differential processing of amyloid precursor protein in brain and in peripheral blood leukocytes

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