Identifying early changes in imaging, plasma, and digital cognitive biomarkers that correspond to Alzheimer's disease pathology in the presence of autopsy‐confirmed co‐pathologies
Year: 2026
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Alzheimer's disease (AD) biomarkers are assessed on their ability to detect AD pathophysiology in vivo, with confirmation of AD neuropathology only at autopsy. METHODS: Positron emission tomography (PET), plasma, and cognitive AD biomarkers were compared to AD neuropathology in Harvard Aging Brain Study participants (10 cognitively unimpaired; 6 mild cognitive impairment). Different PET methods were evaluated, for example, standardized uptake volume ratio (SUVR), distribution volume ratio (DVR), spatial extent (EXT), and partial-volume correction (PVC). RESULTS: F-flortaucipir [FTP]), and plasma tau phosphorylated at threonine 217 (p-tau217) correlate with Aβ plaques (A-score), Braak tau neurofibrillary tangle (NFT) stage (B-score), and neuritic plaques (C-score), whereas plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and cognitive measures did not; although digital Clock Drawing Test (dCDT) latency features did, in an exploratory comparison. Correlations were stronger for Aβ-PET DVR and Aβ-PET EXT (than SUVR with/without PVC) and tau-PET SUVR (composite reference and PVC). DISCUSSION: These findings support the innovative use of imaging, plasma, and digital cognitive tools for detecting AD pathophysiology in a largely cognitively unimpaired population. HIGHLIGHTS: Amyloid beta-positron emission tomography (Aβ-PET), tau-PET imaging, and plasma tau phosphorylated at threonine 217 (p-tau217) correlate with ABC scores Correlations were larger for Aβ-PET distribution volume ratio (DVR) and tau-PET standardized uptake volume ratio (SUVR; composite reference, partial volume correction [PVC]) Digital Clock Drawing Test latency features correlate with A- and Cscores Standard cognitive measures mostly did not correlate with ABC scores Plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) biomarkers did not correlate with ABC scores.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71092
Authors: Charles D. Chen, Cinthya Aguero, Alexandra Melloni, Brian C. Healy, Emma G. Thibault, Jessie Fanglu Fu, Michelle E. Farrell, Stephanie Schultz, Hyun‐Sik Yang, Jean‐Pierre Bellier, Jasmeer Chhatwal, Pia Kivisäkk Webb, Steven Arnold, Dana Penney, Randall Davis, Dorene Rentz, Teresa Gomez‐Isla, Reisa A. Sperling, Keith A. Johnson, Julie C. Price
Institutions: Harvard University, Massachusetts General Hospital, Brigham and Women's Hospital, Tufts University, Lahey Hospital and Medical Center, University of Massachusetts Chan Medical School, Lahey Medical Center, MIT Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Awards: G1458344313, G1523888516, The Mobile Toolbox for Monitoring Cognitive and Behavioral Function (MTB2), Identifying variations in gamma-secretase function that are critical determinants of clinical and biomarker progression of Autosomal Dominant Alzheimer's disease: From mechanism to clinical trials, G9000032698, G9000035911, G9000053885, G9000063280, G9000114674, G9000126385, G9000208313, G9000229375, G9000319018, G9000355232, Program to enrich translation and multimodal research in Alzheimers disease and related dementias
OpenAlex ID: W7119484390