Plasma Amyloid-β Biomarker Associated with Cognitive Decline in Preclinical Alzheimer’s Disease

Article type: Research Article

Authors: Lim, Yen Ying^{a; b; *} | Maruff, Paul^{a; c} | Kaneko, Naoki^d | Doecke, James^e | Fowler, Christopher^a | Villemagne, Victor L.^{a; f} | Kato, Takashi^{g; h} | Rowe, Christopher C.^{a; f} | Arahata, Yutaka^h | Iwamoto, Shinichi^c | Ito, Kengo^{g; h} | Tanaka, Koichi^d | Yanagisawa, Katsuhiko^g | Masters, Colin L.^a | Nakamura, Akinori^g

Affiliations: [a] The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia | [b] The Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC, Australia | [c] Cogstate Ltd., Melbourne, VIC, Australia | [d] Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, Kyoto, Japan | [e] Health and Biosecurity, CSIRO, Brisbane, Australia | [f] Austin Health, Department of Molecular Imaging and Therapy, Center for PET, Heidelberg, VIC, Australia | [g] Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [h] National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan

Correspondence: [*] Correspondence to: Yen Ying Lim, PhD, Level 6, 18 Innovation Walk, Clayton, VIC 3800, Australia. Tel.: +61 3 9035 3000; Fax: +61 3 9035 3107; E-mail: [email protected].

Abstract: Background:Using immunoprecipitation-mass spectrometry, we recently developed and validated a plasma composite biomarker for the assessment of amyloid-β (Aβ) levels. However, as yet, its relationship with clinical outcomes remains unclear. Objective:We aimed to examine the relationship between this plasma Aβ composite biomarker and cognitive function in cognitively normal older adults in two independent cohorts. Methods:Participants enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study and the National Centre for Geriatrics and Gerontology (NCGG) study had undergone Aβ neuroimaging using positron emission tomography (PET), cognitive assessments and provided blood samples. We derived a high-performance plasma Aβ composite biomarker by immunoprecipitation with mass-spectrometry. Results:Both continuous and categorical measures of the plasma Aβ composite biomarker were significantly related to decline in episodic memory and executive function. The magnitude of effects of the plasma Aβ composite on episodic memory and executive function were comparable to that observed for the effects of PET Aβ levels on these same outcome measures. Conclusion:Several plasma Aβ biomarkers have been developed, but none have yet been applied to investigate their relationship with cognitive outcomes. Our results have important implications for the use of this biomarker in the detection of at-risk individuals.

Keywords: Amyloid-β , cognition, memory, plasma, plasma biomarker, preclinical Alzheimer’s disease

DOI: 10.3233/JAD-200475

Journal: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 1057-1065, 2020