Associations of Plasma Tau with Amyloid and Tau PET: Results from the Community-Based Framingham Heart Study

Article type: Research Article

Authors: Ramos-Cejudo, Jaime^{a; *} | Scott, Matthew R.^b | Tanner, Jeremy A.^c | Pase, Matthew P.^{d; e} | McGrath, Emer R.^{f; g; h} | Ghosh, Saptaparni^g | Osorio, Ricardo S.^a | Thibault, Emmaⁱ | El Fakhri, Georgesⁱ | Johnson, Keith A.^{i; j} | Beiser, Alexa^{b; g; k} | Seshadri, Sudha^{c; g; k; *}

Affiliations: [a] Department of Psychiatry, New York University (NYU) Grossman School of Medicine, New York, NY, USA | [b] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA | [c] Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA | [d] Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC, Australia | [e] Harvard T.H. Chan School of Public Health, Boston, MA, USA | [f] HRB Clinical Research Facility, University of Galway, Galway, Ireland | [g] The Framingham Study, Boston, MA, USA | [h] School of Medicine, University of Galway, Galway, Ireland | [i] Department of Radiology, Harvard Medical School, Boston, MA, USA | [j] Department of Neurology, Harvard Medical School, Boston, MA, USA | [k] Department of Neurology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA

Correspondence: [*] Correspondence to: Dr. Jaime Ramos-Cejudo, NYU Grossman School of Medicine, Division of Brain Aging, 145 East 32nd Street, New York, NY 10016, USA. Tel.: +1 212 263 3255; E-mail jaime.ramoscejudo@nyulangone.org and Dr. Sudha Seshadri, University of Texas Health Sciences Center, 7703 Floyd Curl Drive, Mail Code 8070, San Antonio, TX 78229, USA. Tel.: +1 210 450 8437; E-mail seshadri@uthscsa.edu.

Abstract: Background:Associations of plasma total tau levels with future risk of AD have been described. Objective:To examine the extent to which plasma tau reflects underlying AD brain pathology in cognitively healthy individuals. Methods:We examined cross-sectional associations of plasma total tau with 11C-Pittsburgh Compound-B (PiB)-PET and 18F-Flortaucipir (FTP)-PET in middle-aged participants at the community-based Framingham Heart Study. Results:Our final sample included 425 participants (mean age 57.6± 9.9, 50% F). Plasma total tau levels were positively associated with amyloid-β deposition in the precuneus region (β±SE, 0.11±0.05; p = 0.025). A positive association between plasma total tau and tau PET in the rhinal cortex was suggested in participants with higher amyloid-PET burden and in APOE ɛ4 carriers. Conclusions:Our study highlights that plasma total tau is a marker of amyloid deposition as early as in middle-age.

Keywords: Alzheimer’s disease, amyloid-β, Framingham Heart Study, PET, plasma total tau, tau

DOI: 10.3233/JAD-231320

Journal: Journal of Alzheimer's Disease, vol. 100, no. 2, pp. 487-494, 2024