Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer's disease

被引：53

作者：

Crist, Angela M. ^{[1
]}

Hinkle, Kelly M. ^{[1
]}

Wang, Xue ^{[2
]}

Moloney, Christina M. ^{[1
]}

Matchett, Billie J. ^{[1
]}

Labuzan, Sydney A. ^{[1
]}

Frankenhauser, Isabelle ^{[1
,3
]}

Azu, Nkem O. ^{[1
]}

Liesinger, Amanda M. ^{[1
]}

Lesser, Elizabeth R. ^{[2
]}

Serie, Daniel J. ^{[2
]}

Quicksall, Zachary S. ^{[2
]}

Patel, Tulsi A. ^{[1
]}

Carnwath, Troy P. ^{[1
]}

DeTure, Michael ^{[1
]}

Tang, Xiaojia ^{[4
]}

Petersen, Ronald C. ^{[5
]}

Duara, Ranjan ^{[6
]}

Graff-Radford, Neill R. ^{[7
]}

Allen, Mariet ^{[1
]}

Carrasquillo, Minerva M. ^{[1
]}

Li, Hu ^{[8
]}

Ross, Owen A. ^{[1
]}

Ertekin-Taner, Nilufer ^{[1
,7
]}

Dickson, Dennis W. ^{[1
]}

Asmann, Yan W. ^{[2
]}

Carter, Rickey E. ^{[2
]}

Murray, Melissa E. ^{[1
]}

机构：

[1] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA

[2] Mayo Clin, Dept Hlth Sci Res, Jacksonville, FL 32224 USA

[3] Paracelsus Med Private Univ, Salzburg, Austria

[4] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[5] Mayo Clin, Dept Neurol, Rochester, MN USA

[6] Mt Sinai Med Ctr, Wien Ctr Alzheimers Dis & Memory Disorders, Miami Beach, FL 33140 USA

[7] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[8] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

PROTEIN-C INHIBITOR; NEUROPATHOLOGICALLY DEFINED SUBTYPES; GENOME-WIDE ASSOCIATION; DEATH EFFECTOR DOMAIN; NEUROFIBRILLARY TANGLES; NUCLEAR-LOCALIZATION; COMMON VARIANTS; HUMAN BRAIN; EARLY-ONSET; TAU PET;

D O I：

10.1038/s41467-021-22399-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer's disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.

引用

页数：17

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