Ultrasensitive Detection of Plasma Amyloid-β as a Biomarker for Cognitively Normal Elderly Individuals at Risk of Alzheimer’s Disease

Article type: Research Article

Authors: Chatterjee, Pratishtha^{a; b} | Elmi, Mitra^a | Goozee, Kathryn^{a; b; c; d; e; g} | Shah, Tejal^{a; b; f} | Sohrabi, Hamid R.^{a; b; e; f} | Dias, Cintia B.^{a; h} | Pedrini, Steve^b | Shen, Kaikaiⁱ | Asih, Prita R.^a | Dave, Preeti^{a; d; j} | Taddei, Kevin^{b; f} | Vanderstichele, Hugo^{k; l} | Zetterberg, Henrik^{m; n; o; p} | Blennow, Kaj^{m; n} | Martins, Ralph N.^{a; b; c; e; f; g; *}

Affiliations: [a] Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia | [b] School of Medical Health and Sciences, Edith Cowan University, Joondalup, WA, Australia | [c] KaRa Institute of Neurological Disease, Sydney, Macquarie Park, Australia | [d] Anglicare, Sydney, Castle Hill, NSW, Australia | [e] School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia | [f] Australian Alzheimer’s Research Foundation, Nedlands, WA, Australia | [g] The Cooperative Research Centre for Mental Health, Carlton South, Australia | [h] School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, NSW, Australia | [i] Australian eHealth Research Centre, CSIRO, Floreat, Australia | [j] John Curtin School of Medical research, Canberra, Australia | [k] ADx NeuroSciences, Gent, Belgium | [l] Biomarkable, Gent, Belgium | [m] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden | [n] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [o] Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, United Kingdom | [p] UK Dementia Research Institute at UCL, London, United Kingdom

Correspondence: [*] Correspondence to: Professor Ralph N. Martins, School of Medical and Health Sciences, Edith Cowan University, Ralph & Patricia Sarich Neuroscience Research Institute, 8 Verdun Street, Nedlands, WA 6009, Australia. Tel.: +61 618 6304 5456; Fax: +61 618 6304 5851; E-mail: r.martins@ecu.edu.au.

Abstract: Background:Aberrant amyloid-β (Aβ) deposition in the brain occurs two decades prior to the manifestation of Alzheimer’s disease (AD) clinical symptoms and therefore brain Aβ load measured using PET serves as a gold standard biomarker for the early diagnosis of AD. However, the uneconomical nature of PET makes blood markers, that reflect brain Aβ deposition, attractive candidates for investigation as surrogate markers. Objective:Investigation of plasma Aβ as a surrogate marker for brain Aβ deposition in cognitively normal elderly individuals. Methods:Plasma Aβ40 and Aβ42 concentrations were measured using the ultrasensitive Single Molecule Array (Simoa) assay in 95 cognitively normal elderly individuals, who have all undergone PET to assess brain Aβ deposition. Based on the standard uptake value ratios (SUVR) obtained from PET imaging, using the tracer 18F-Florbetaben, plasma Aβ was compared between 32 participants assessed to have low brain Aβ load (Aβ–, SUVR <1.35) and 63 assessed to have high brain Aβ load (Aβ+, SUVR ≥1.35). Results:Plasma Aβ42/Aβ40 ratios were lower in the Aβ+ group compared to the Aβ–group. Plasma Aβ40 and Aβ42 levels were not significantly different between Aβ–and Aβ+ groups, although a trend of higher plasma Aβ40 was observed in the Aβ+ group. Additionally, plasma Aβ42/Aβ40 ratios along with the known AD risk factors, age and APOE ɛ4 status, resulted in Aβ+ participants being distinguished from Aβ–participants based on an area under the receiver operating characteristic curve shown to be 78%. Conclusion:Plasma Aβ ratios in this study are a potential biomarker for brain Aβ deposition and therefore, for preclinical AD. However, this method to measure plasma Aβ needs further development to increase the accuracy of this promising AD blood biomarker.

Keywords: Alzheimer’s disease, blood biomarkers, plasma amyloid-β, plasma amyloid-β ratios, preclinical Alzheimer’s disease, single molecule array

DOI: 10.3233/JAD-190533

Journal: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 775-783, 2019