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

Jan 8, 2026Alzheimer's & dementia : the journal of the Alzheimer's Association

Early imaging, blood, and digital cognitive signs linked to Alzheimer's brain changes when other diseases are also present

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Abstract

Amyloid beta-PET, tau-PET, and plasma tau phosphorylated at threonine 217 correlate with Alzheimer's disease pathology scores.

Aβ-PET and tau-PET imaging show significant correlation with amyloid plaques and tau neurofibrillary tangles.
Stronger correlations are observed with Aβ-PET distribution volume ratio and tau-PET standardized uptake volume ratio compared to other methods.
Digital Clock Drawing Test latency features have a correlation with amyloid and neuritic plaque scores.
Standard cognitive measures generally do not correlate with Alzheimer's disease pathology scores.
Plasma biomarkers glial fibrillary acidic protein and neurofilament light chain do not show correlation with Alzheimer's disease pathology scores.

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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: Amyloid beta (Aβ)-PET (C-Pittsburgh compound B [PiB]), tau-PET (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). 11 18

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.

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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

Abstract

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