Plasma Amyloid and in vivo Brain Amyloid in Late Middle-Aged Hispanics

Article type: Research Article

Authors: Rippon, Brady^a | Palta, Priya^{a; b} | Tahmi, Mouna^a | Sherwood, Greysi^a | Soto, Luisa^a | Cespedes, Sandino^a | Mesen, Yanette^a | He, Hengda^c | Laing, Krystal^d | Moreno, Herman^h | Teresi, Jeanne^g | Razlighi, Qolamrezaⁱ | Brickman, Adam M.^{c; d; e} | Zetterberg, Henrik^j | Luchsinger, José A.^{a; b; *}

Affiliations: [a] Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center (CUIMC), New York, NY, USA | [b] Department of Epidemiology, Joseph P. Mailman School of Public Health, CUIMC, New York, NY, USA | [c] Department of Neurology, College of Physicians and Surgeons, CUIMC, New York, NY, USA | [d] Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, CUIMC, New York, NY, USA | [e] Gertrude H. Sergievsky Center, CUIMC, New York, NY, USA | [f] Department of Biomedical Engineering, Columbia University, New York, NY, USA | [g] Research Division, Hebrew Home in Riverdale, Bronx, NY, USA | [h] Department of Neurology and Pharmacology/Physiology, SUNY Downstate Medical Center, Brooklyn, NY, USA | [i] Department of Radiology, Weill Cornell Medical College, New York, NY, USA | [j] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [k] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [l] Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom | [m] UK Dementia Research Institute at UCL, London, United Kingdom

Correspondence: [*] Correspondence to: Jose A. Luchsinger, MD MPH, Columbia University Irving Medical Center, 622 West 168^th Street, PH9 Center room 210, New York, NY 10032, USA. Tel.: +1 212 305 4730; Fax: +1 212 305 9349; E-mail: [email protected].

Abstract: Background:Determining amyloid positivity is possible with cerebrospinal fluid and brain imaging of amyloid, but these methods are invasive and expensive. Objective:To relate plasma amyloid-β (Aβ), measured using Single-molecule array (Simoatrademark) assays, to in vivo brain Aβ, measured using positron emission tomography (PET), examine the accuracy of plasma Aβ to predict brain Aβ positivity, and the relation of APOE ɛ4 with plasma Aβ. Methods:We performed a cross-sectional analysis in a cohort of 345 late middle-aged Hispanic men and women (age 64 years, 72% women). Our primary plasma variable was Aβ42/Aβ40 ratio measured with Simoa. Brain Aβ burden was measured as global SUVR with 18F-Florbetaben PET examined continuously and categorically. Results:Plasma Aβ42/Aβ40 ratio was inversely associated with global Aβ SUVR (β= –0.13, 95% Confidence Interval (CI): –0.23, –0.03; p = 0.013) and Aβ positivity (Odds Ratio: 0.59, 95% CI: 0.38, 0.91; p = 0.016), independent of demographics and APOE ɛ4. ROC curves (AUC = 0.73, 95% CI: 0.64, 0.82; p < 0.0001) showed that the optimal threshold for plasma Aβ42/Aβ40 ratio in relation to brain Aβ positivity was 0.060 with a sensitivity of 82.4% and specificity of 62.8%. APOE ɛ4 carriers had lower Aβ42/Aβ40 ratio and a higher Aβ positivity determined with the Aβ42/Aβ40 ratio threshold of 0.060. Conclusion:Plasma Aβ42/Aβ40 ratio assayed using Simoa is weakly correlated with in vivo brain amyloid and has limited accuracy in screening for amyloid positivity and for studying risk factors of brain amyloid burden when in vivo imaging is not feasible.

Keywords: Alzheimer’s disease, amyloid, brain, hispanics, middle age, plasma, positron emission tomography

DOI: 10.3233/JAD-210391

Journal: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1229-1238, 2022