Research Article of International Journal of Aging Research
Diagnosis and monitoring of Alzheimer Disease with saliva biomarker BACE1
Dr SJ Kellner and Prof M Ferchichi
Mesencell Biotech International Ltd, 20-22 Wenlock Road, London, N1 7GU, United Kingdom
Alzheimer’s disease (AD) is characterized by the slow decline of cognition and functional abilities over time. The diagnosis for probable and possible AD relies principally on clinical criteria. The confirmation of the disease is made post-mortem by identifying extracellular senile plaques and intraneuronal fibrillary tangles in the brains of subjects with clinically defined dementia. However, the field critically lacks validated AD specific peripheral biomarkers to support the diagnosis in living patients or for early detection of patients at risk before symptoms appear. BACE1 (Beta site amyloid precursor protein cleaving enzyme 1) cleaves Amyloid Precursor Protein (APP) at two beta sites and represents a key target enzyme in the monitoring and possible treatment of AD. In our preliminary study, we evaluated the usefulness of salivary BACE1 to determine risk to develop AD in clinically normal patients. A preliminary in house laboratory grading system for BACE1 content in saliva was established with high levels of salivary BACE1 present in older patients and putatively at risk to develop AD. BACE1 seems to be a useful biomarker to help diagnose AD and to monitor disease progression, and remarkably regression, when treated with stem cell secretome.
Keywords:Biomarkers, Alzheimer Disease, Mesenchymal stem cells, amyloid beta, amyloid precursor protein, amyloid plaques, BACE1, neprilysin, micro RNA, UHC-L1, disease monitoring, saliva
How to cite this article:
SJ Kellner and M Ferchichi. Diagnosis and monitoring of Alzheimer Disease with saliva biomarker BACE1. International Journal of Aging Research, 2018, 1:21. DOI: 10.28933/ijoar-2018-10-0909
1. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011; 7:263–269. [PubMed: 21514250]
2. Yanhong Zhou, Chuangchuang Tan, Dong Wen, Hongmin Sun, Wei Han and Yuchen Xu: The Biomarkers for Identifying Preclinical Alzheimer’s Disease via Structural and Functional Magnetic. Front. Aging Neurosci., 27 April 2016 | https://doi.org/10.3389/fnagi.2016.00092
3. Koyama A, Okereke OI, Yang T, Blacker D, Selkoe DJ, Grodstein F. Plasma Amyloid-beta as a Predictor of Dementia and Cognitive Decline: A Systematic Review and Meta-analysis. Arch Neurol.2012
4. Selkoe D. J. (2011) Alzheimer’s Disease. Cold Spring Harb. Perspect. Biol. 3, a004457
5. Bayer T. A. and Wirths O. (2010) Intracellular accumulation of amyloidBeta – a predictor for synaptic dysfunction and neuron loss in Alzheimer’s disease. Front. Aging Neurosci. 2, 8.
6. Roberds S. L., Anderson J. and Basi G. et al. (2001) BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer’s disease therapeutics. Hum. Mol. Genet. 10, 1317–1324.
7. Sun X., He G. and Song W. (2006a) BACE2, as a novel APP thetasecretase, is not responsible for the pathogenesis of Alzheimer’s disease in Down syndrome. FASEB J. 20, 1369–1376.
8. Kathryn M. Munro, Amelia Nash, Martina Pigoni, Stefan F. Lichtenthaler & Jenny M. Gunnersen. Functions of the Alzheimer’s Disease Protease BACE1 at the Synapse in the Central Nervous System. J Mol Neurosci (2016) 60:305–315
9. Latha Devi and Masuo Ohnu. A combination Alzheimer’s therapy targeting BACE1 and Neprilysin in 5XFAD transgenic mice. Molecular Brain (2015) 8:19
10. Mingming Zhang et al..Control of BACE1 degradation and APP processing by ubiquitin carboxyl-terminal hydrolase L1. Journal of Neurochemistry, 2012, 120:1129-1138
11. Lundgren et al.. ADAM10 and BACE1 are localized to synaptic vesicles. Journal of Neurochemistry 2015, 135, 606-615
12. Tramutola et al., 2016: It is all about Ubiquitin: Role of altered Ubiquitin-Proteasome System and UCHL1 in Alzheimer Disease. Oxidative Medicine and Longevity Vol 2016, ArtID2756068
13. Gong et al., 2016: The Ubiquitin-Proteasome System: Potential Therapeutic Targets for Alzheimer Disease and Spinal Cord Injury. Front.Mol.Neurosci.9:4
This work and its PDF file(s) are licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.