Amyloid and tau-PET in early-onset AD: Baseline data from the Longitudinal Early-onset Alzheimer's Disease Study (LEADS).

Abstract

INTRODUCTION:

We aimed to describe baseline amyloid-beta (Aβ) and tau-positron emission tomograrphy (PET) from Longitudinal Early-onset Alzheimer's Disease Study (LEADS), a prospective multi-site observational study of sporadic early-onset Alzheimer's disease (EOAD).

METHODS:

We analyzed baseline [18F]Florbetaben (Aβ) and [18F]Flortaucipir (tau)-PET from cognitively impaired participants with a clinical diagnosis of mild cognitive impairment (MCI) or AD dementia aged < 65 years. Florbetaben scans were used to distinguish cognitively impaired participants with EOAD (Aβ+) from EOnonAD (Aβ-) based on the combination of visual read by expert reader and image quantification.

RESULTS:

243/321 (75.7%) of participants were assigned to the EOAD group based on amyloid-PET; 231 (95.1%) of them were tau-PET positive (A+T+). Tau-PET signal was elevated across cortical regions with a parietal-predominant pattern, and higher burden was observed in younger and female EOAD participants.

DISCUSSION:

LEADS data emphasizes the importance of biomarkers to enhance diagnostic accuracy in EOAD. The advanced tau-PET binding at baseline might have implications for therapeutic strategies in patients with EOAD.

HIGHLIGHTS:

72% of patients with clinical EOAD were positive on both amyloid- and tau-PET. Amyloid-positive patients with EOAD had high tau-PET signal across cortical regions. In EOAD, tau-PET mediated the relationship between amyloid-PET and MMSE. Among EOAD patients, younger onset and female sex were associated with higher tau-PET.

• Authors: Hanna Cho, Nidhi S Mundada, Liana G Apostolova, Maria C Carrillo, Ranjani Shankar, Alinda N Amuiri, Ehud Zeltzer, Charles C Windon, David N Soleimani-Meigooni, Jeremy A Tanner, Courtney Lawhn Heath, Orit H Lesman-Segev, Paul Aisen, Ani Eloyan, Hye Sun Lee, Dustin B Hammers, Kala Kirby, Jeffrey L Dage, Anne Fagan, Tatiana Foroud, Lea T Grinberg, Clifford R Jack, Joel Kramer, Walter A Kukull, Melissa E Murray, Kelly Nudelman, Arthur Toga, Prashanthi Vemuri, Alireza Atri, Gregory S Day, Ranjan Duara, Neill R Graff-Radford, Lawrence S Honig, David T Jones, Joseph Masdeu, Mario Mendez, Erik Musiek, Chiadi U Onyike, Meghan Riddle, Emily J Rogalski, Stephen Salloway, Sharon Sha, Raymond Scott Turner, Thomas S Wingo, David A Wolk, Robert Koeppe, Leonardo Iaccarino, Bradford C Dickerson, Renaud La Joie, Gil D Rabinovici, LEADS Consortium
• Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association (Alzheimers Dement) Vol. 19 Suppl 9 Pg. S98-S114 (11 2023) ISSN: 1552-5279 [Electronic] United States
• PMID: 37690109 (Publication Type: Observational Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Chemical References

• 4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene
• tau Proteins
• Amyloid beta-Peptides
• Amyloid
• Biomarkers

Topics

• Humans
• Female
• Alzheimer Disease (metabolism)
• Electrons
• Prospective Studies
• tau Proteins (metabolism)
• Positron-Emission Tomography (methods)
• Amyloid beta-Peptides (metabolism)
• Cognitive Dysfunction (diagnostic imaging, metabolism)
• Amyloid (metabolism)
• Biomarkers