Lower Plasma Amyloid Beta - 42 Levels Associated With Worse Survival in Patients With Glioma

Overview

Journal In Vivo

Specialty Oncology

Date 2023 Dec 26

PMID 38148047

Authors

Kyeongjin Seo

Kihwan Hwang

Minhee Noh

Jay Park

Kwang-Sung Ahn

So Young Ji

Jung Ho Han

Chae-Yong Kim

Affiliations

Soon will be listed here.

Abstract

Background/aim: Glioma is often refractory. The accumulation of amyloid beta (Aβ) in the brain is commonly associated with Alzheimer's disease (AD), but there are studies suggesting that Aβ has tumor suppressor potential. The aim of this study was to identify a novel, non-invasive candidate biomarker for histological prediction and prognostic assessment of glioma.

Patients And Methods: Serum was prepared from blood samples collected preoperatively from 48 patients with WHO grade II-IV glioma between October 2004 and December 2017 at a single tertiary institution. The concentration of Aβ42 was measured using the SMCxPRO immunoassay (Merck). The clinical and histological characteristics of the patients, including molecular subtypes, were reviewed.

Results: The mean age of the patients was 52.2±12.5 years. The mean value of serum Aβ42 concentration was 7.6±7.8 pg/ml in the anaplastic astrocytoma (WHO grade III) group and 6.4±6.5 pg/ml in the glioblastoma multiforme (WHO grade IV) group. The Negative epidermal growth factor receptor (EGFR) expression was associated with higher serum Aβ42 levels (p=0.020). Kaplan-Meier analysis demonstrated that patients with high serum Aβ42 (>11.78 pg/ml) had significantly longer progression-free survival (PFS) (p=0.038) and overall survival (OS) (p=0.018).

Conclusion: This study investigated serum Aβ42 levels as a potential biomarker for glioma. The results showed that low serum Aβ42 levels were associated with EGFR expression and poor PFS and OS. Overall, these findings suggest a potential role of Aβ42 as a prognostic marker in astrocytomas.

References

Zayas-Santiago A, Diaz-Garcia A, Nunez-Rodriguez R, Inyushin M . Accumulation of amyloid beta in human glioblastomas. Clin Exp Immunol. 2020; 202(3):325-334. PMC: 7670151. DOI: 10.1111/cei.13493. View

Kent S, Spires-Jones T, Durrant C . The physiological roles of tau and Aβ: implications for Alzheimer's disease pathology and therapeutics. Acta Neuropathol. 2020; 140(4):417-447. PMC: 7498448. DOI: 10.1007/s00401-020-02196-w. View

Gagni P, Sola L, Cretich M, Chiari M . Development of a high-sensitivity immunoassay for amyloid-beta 1-42 using a silicon microarray platform. Biosens Bioelectron. 2013; 47:490-5. DOI: 10.1016/j.bios.2013.03.077. View

Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister S . Glioma. Nat Rev Dis Primers. 2016; 1:15017. DOI: 10.1038/nrdp.2015.17. View

Musicco M, Adorni F, Di Santo S, Prinelli F, Pettenati C, Caltagirone C . Inverse occurrence of cancer and Alzheimer disease: a population-based incidence study. Neurology. 2013; 81(4):322-8. DOI: 10.1212/WNL.0b013e31829c5ec1. View

van Bodegraven E, van Asperen J, Robe P, Hol E . Importance of GFAP isoform-specific analyses in astrocytoma. Glia. 2019; 67(8):1417-1433. PMC: 6617972. DOI: 10.1002/glia.23594. View

Blasko I, Jellinger K, Kemmler G, Krampla W, Jungwirth S, Wichart I . Conversion from cognitive health to mild cognitive impairment and Alzheimer's disease: prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine. Neurobiol Aging. 2006; 29(1):1-11. DOI: 10.1016/j.neurobiolaging.2006.09.002. View

Park S, Lee S, Hong Y, Hwang S, Lee J, Bang S . Suppressive effects of SuHeXiang Wan on amyloid-β42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer's disease. Biol Pharm Bull. 2012; 36(3):390-8. DOI: 10.1248/bpb.b12-00792. View

Durrant C, Ruscher K, Sheppard O, Coleman M, Ozen I . Beta secretase 1-dependent amyloid precursor protein processing promotes excessive vascular sprouting through NOTCH3 signalling. Cell Death Dis. 2020; 11(2):98. PMC: 7005019. DOI: 10.1038/s41419-020-2288-4. View

10.

Brothers H, Gosztyla M, Robinson S . The Physiological Roles of Amyloid-β Peptide Hint at New Ways to Treat Alzheimer's Disease. Front Aging Neurosci. 2018; 10:118. PMC: 5996906. DOI: 10.3389/fnagi.2018.00118. View

11.

Camara-Quintana J, Nitta R, Li G . Pathology: commonly monitored glioblastoma markers: EFGR, EGFRvIII, PTEN, and MGMT. Neurosurg Clin N Am. 2012; 23(2):237-46, viii. DOI: 10.1016/j.nec.2012.01.011. View

12.

Goodenberger M, Jenkins R . Genetics of adult glioma. Cancer Genet. 2012; 205(12):613-21. DOI: 10.1016/j.cancergen.2012.10.009. View

13.

Oda K, Matsuoka Y, Funahashi A, Kitano H . A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol. 2006; 1:2005.0010. PMC: 1681468. DOI: 10.1038/msb4100014. View

14.

Biron K, Dickstein D, Gopaul R, Jefferies W . Amyloid triggers extensive cerebral angiogenesis causing blood brain barrier permeability and hypervascularity in Alzheimer's disease. PLoS One. 2011; 6(8):e23789. PMC: 3166122. DOI: 10.1371/journal.pone.0023789. View

15.

Wang L, Liang B, Zhong Y . Reduced EGFR level potentially mediates the Aβ42-induced neuronal loss in transgenic fruit fly and mouse. Protein Cell. 2013; 4(9):647-9. PMC: 4875527. DOI: 10.1007/s13238-013-3043-8. View

16.

Desai B, Schneider J, Li J, Carvey P, Hendey B . Evidence of angiogenic vessels in Alzheimer's disease. J Neural Transm (Vienna). 2009; 116(5):587-97. PMC: 2753398. DOI: 10.1007/s00702-009-0226-9. View

17.

Shibata M, Yamada S, Kumar S, Calero M, Bading J, Frangione B . Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest. 2000; 106(12):1489-99. PMC: 387254. DOI: 10.1172/JCI10498. View

18.

Bonosi L, Ferini G, Giammalva G, Benigno U, Porzio M, Giovannini E . Liquid Biopsy in Diagnosis and Prognosis of High-Grade Gliomas; State-of-the-Art and Literature Review. Life (Basel). 2022; 12(3). PMC: 8950809. DOI: 10.3390/life12030407. View

19.

Figarella-Branger D, Appay R, Metais A, Tauziede-Espariat A, Colin C, Rousseau A . [The 2021 WHO classification of tumours of the central nervous system]. Ann Pathol. 2021; 42(5):367-382. DOI: 10.1016/j.annpat.2021.11.005. View

20.

Pandey V, Bhaskara V, Prakash Babu P . Implications of mitogen-activated protein kinase signaling in glioma. J Neurosci Res. 2015; 94(2):114-27. DOI: 10.1002/jnr.23687. View