Molecular characterization of selectively vulnerable neurons in Alzheimer's disease.
IF: 28.771
Cited by: 187


Alzheimer's disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus-brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively-from postmortem brains spanning the progression of AD-type tau neurofibrillary pathology. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience.


Spatial Transcriptomics
Gene Expression

MeSH terms

Aged, 80 and over
Alzheimer Disease
Entorhinal Cortex
Frontal Lobe
Middle Aged
Neurofibrillary Tangles
tau Proteins


Leng, Kun
Li, Emmy
Eser, Rana
Piergies, Antonia
Sit, Rene
Tan, Michelle
Neff, Norma
Li, Song Hua
Rodriguez, Roberta Diehl
Suemoto, Claudia Kimie
Leite, Renata Elaine Paraizo
Ehrenberg, Alexander J
Pasqualucci, Carlos A
Seeley, William W
Spina, Salvatore
Heinsen, Helmut
Grinberg, Lea T
Kampmann, Martin

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