Correlating hippocampal and amygdala volumes with neuropathological burden in Down syndrome and Alzheimer’s disease and related neurodegenerative pathologies using 7T postmortem MRI

作者：Jr‐Jiun Liou, Jinghang Li, Jacob Berardinelli, Hecheng Jin, Tales Santini, Jaehoon Noh, Nadim Farhat, Minjie Wu, Howard Aizenstein, Joseph Mettenburg, William H. Yong, Elizabeth Head, Miloš D. Ikonomović, Tamer S. Ibrahim, Julia Kofler, Beau M. Ances, Howard Andrews, Karen L. Bell, Rasmus M. Birn, Adam M. Brickman, Peter Bulova, Amrita K. Cheema, Kewei Chen, Bradley T. Christian, I. C. H. Clare, Lorraine N. Clark, Ann D. Cohen, John N. Constantino, Eric Doran, Anne M. Fagan, Eleanor Feingold, Tatiana Foroud, Benjamin L. Handen, Sigan L. Hartley, Rachel L. Henson, Christy Hom, Lawrence S. Honig, Sterling C. Johnson, Courtney Jordan, M. Ilyas Kamboh, David B. Keator, William E. Klunk, William Charles Kreisl, Sharon J. Krinsky‐McHale, Florence Lai, Patrick J. Lao, Charles M. Laymon, Joseph H. Lee, Ira T. Lott, Victoria Lupson, Mark Mapstone, Chester A. Mathis, Davneet Minhas, Neelesh Nadkarni, Sid E. O’Bryant, Deborah Pang, Melissa Petersen, Julie C. Price, Margaret Pulsifer, Michael S. Rafii, Eric M. Reiman, Batool Rizvi, H. Diana Rosas, Marwan N. Sabbagh, Nicole Schupf, Wayne Silverman, Dana Tudorascu, Rameshwari V. Tumuluru, Benjamin Tycko, Badri Varadarajan, Desirée A. White, Michael A. Yassa, Shahid Zaman, Fan Zhang · 发表于：Journal of Neuropathology & Experimental Neurology · 年份：2025 · DOI：10.1093/jnen/nlaf010 · 被引用次数：7 · 研究领域：Dementia and Cognitive Impairment Research、Alzheimer's disease research and treatments、Advanced Neuroimaging Techniques and Applications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), is common in elderly brains and often seen in conjunction with Alzheimer's disease neuropathologic change (ADNC). LATE-NC typically begins in the amygdala and spreads to the hippocampus and neocortex. Whether it contributes to hippocampal and amygdala atrophy in Down syndrome (DS) remains unexplored. We analyzed amygdala and hippocampal volumes and neuropathological burden in 12 DS cases and 54 non-DS cases with AD and related neurodegenerative pathologies (ADRNP) using 7 Tesla (7T) postmortem ex vivo MRI. Postmortem and antemortem hippocampal volumes were significantly correlated in a subset of 17 cases with available antemortem MRI scans. DS cases had smaller hippocampal and amygdala volumes than ADRNP cases; these correlated with more severe Braak stage but not with Thal phase. LATE-NC and hippocampal sclerosis (HS) were uncommon in DS cases. In ADRNP cases, lower hippocampal volumes associated with dementia duration, advanced Thal phase, Braak NFT stage, C score, LATE-NC stage, HS and arteriolosclerosis severity; reduced amygdala volumes correlated with severe LATE-NC stage, HS, and arteriolosclerosis severity, but not with Thal phase or Braak NFT stage. Lewy body pathology did not affect hippocampal or amygdala volume in either cohort. Thus, hippocampal volumes in ADRNP were influenced by both ADNC and LATE-NC, and amygdala volumes were primarily influenced by LATE-NC. In DS, hippocamp...