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Thalamic nuclei insights into Alzheimer's disease

Vidal, J. P.; Myall, D.; Pariente, J.; Pitcher, T.; Roberts, R. P.; Cawston, E.; Leheron, C.; Anderson, T.; Morgan, C.; Melzer, T.; Kirk, I.; Tippett, L.; Peran, P.; Dalrymple-alford, J.

2026-05-28 neuroscience
10.64898/2026.05.26.728015 bioRxiv
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INTRODUCTIONThalamic nuclei support multiple cognitive processes, yet their integrity in biologically-defined Alzheimers disease (AD) remains unknown. METHODAmyloid status was determined using PET Centiloids >24 in 1,327 participants from ADNI. Combined with clinical diagnosis, this yielded six groups: amyloid-negative or positive CN-MCI-dementia/AD. Thalamic nuclei volumes were extracted from T1-weighted MRI using the HIPS-THOMAS algorithm. RESULTSLarge volume reductions in the anteroventral, mediodorsal, and pulvinar nuclei were observed in amyloid-positive MCI and AD. Reduced volumes were also evident in amyloid-positive CN, supporting preclinical AD. Adding the anteroventral nucleus improved cognitive status classification in Random Forest analyses. A phenotypic model integrating thalamic nuclei clearly distinguished amyloid-positive groups from amyloid-negative CN and reclassified non-AD patients with 68% of amyloid-negative MCI subjects as CN-like, and 27% of amyloid-positive CN as MCI-like. DISCUSSIONThalamic volumetry from conventional T1-weighted MRI enhances clinical insight into AD and provides a practical biomarker for disease intervention.

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