Research ExplorerPublicationsSingle-nucleus RNA sequencing demonstrates an autosomal domi...

Single-nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer's disease profile and possible mechanisms of disease protection

Standard

Single-nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer's disease profile and possible mechanisms of disease protection. / Almeida, Maria Camila; Eger, Sarah J; He, Caroline; Audouard, Morgane; Nikitina, Arina; Glasauer, Stella M K; Han, Dasol; Mejía-Cupajita, Barbara; Acosta-Uribe, Juliana; Villalba-Moreno, Nelson David; Littau, Jessica Lisa; Elcheikhali, Megan; Rivera, Erica Keane; Carrettiero, Daniel Carneiro; Villegas-Lanau, Carlos Andrés; Sepulveda-Falla, Diego; Lopera, Francisco; Kosik, Kenneth S.

In: NEURON, Vol. 112, No. 11, 05.06.2024, p. 1778-1794.e7.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Almeida, MC, Eger, SJ, He, C, Audouard, M, Nikitina, A, Glasauer, SMK, Han, D, Mejía-Cupajita, B, Acosta-Uribe, J, Villalba-Moreno, ND, Littau, JL, Elcheikhali, M, Rivera, EK, Carrettiero, DC, Villegas-Lanau, CA, Sepulveda-Falla, D, Lopera, F & Kosik, KS 2024, 'Single-nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer's disease profile and possible mechanisms of disease protection', NEURON, vol. 112, no. 11, pp. 1778-1794.e7. https://doi.org/10.1016/j.neuron.2024.02.009

APA

Almeida, M. C., Eger, S. J., He, C., Audouard, M., Nikitina, A., Glasauer, S. M. K., Han, D., Mejía-Cupajita, B., Acosta-Uribe, J., Villalba-Moreno, N. D., Littau, J. L., Elcheikhali, M., Rivera, E. K., Carrettiero, D. C., Villegas-Lanau, C. A., Sepulveda-Falla, D., Lopera, F., & Kosik, K. S. (2024). Single-nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer's disease profile and possible mechanisms of disease protection. NEURON, 112(11), 1778-1794.e7. https://doi.org/10.1016/j.neuron.2024.02.009

Vancouver

Almeida MC, Eger SJ, He C, Audouard M, Nikitina A, Glasauer SMK et al. Single-nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer's disease profile and possible mechanisms of disease protection. NEURON. 2024 Jun 5;112(11):1778-1794.e7. https://doi.org/10.1016/j.neuron.2024.02.009

Bibtex

@article{19d7c7df67bc447db97e95de8dbdadf8,
title = "Single-nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer's disease profile and possible mechanisms of disease protection",
abstract = "Highly penetrant autosomal dominant Alzheimer's disease (ADAD) comprises a distinct disease entity as compared to the far more prevalent form of AD in which common variants collectively contribute to risk. The downstream pathways that distinguish these AD forms in specific cell types have not been deeply explored. We compared single-nucleus transcriptomes among a set of 27 cases divided among PSEN1-E280A ADAD carriers, sporadic AD, and controls. Autophagy genes and chaperones clearly defined the PSEN1-E280A cases compared to sporadic AD. Spatial transcriptomics validated the activation of chaperone-mediated autophagy genes in PSEN1-E280A. The PSEN1-E280A case in which much of the brain was spared neurofibrillary pathology and harbored a homozygous APOE3-Christchurch variant revealed possible explanations for protection from AD pathology including overexpression of LRP1 in astrocytes, increased expression of FKBP1B, and decreased PSEN1 expression in neurons. The unique cellular responses in ADAD and sporadic AD require consideration when designing clinical trials.",
author = "Almeida, {Maria Camila} and Eger, {Sarah J} and Caroline He and Morgane Audouard and Arina Nikitina and Glasauer, {Stella M K} and Dasol Han and Barbara Mej{\'i}a-Cupajita and Juliana Acosta-Uribe and Villalba-Moreno, {Nelson David} and Littau, {Jessica Lisa} and Megan Elcheikhali and Rivera, {Erica Keane} and Carrettiero, {Daniel Carneiro} and Villegas-Lanau, {Carlos Andr{\'e}s} and Diego Sepulveda-Falla and Francisco Lopera and Kosik, {Kenneth S}",
note = "Copyright {\textcopyright} 2024 Elsevier Inc. All rights reserved.",
year = "2024",
month = jun,
day = "5",
doi = "10.1016/j.neuron.2024.02.009",
language = "English",
volume = "112",
pages = "1778--1794.e7",
journal = "NEURON",
issn = "0896-6273",
publisher = "Cell Press",
number = "11",

}

RIS

TY - JOUR

T1 - Single-nucleus RNA sequencing demonstrates an autosomal dominant Alzheimer's disease profile and possible mechanisms of disease protection

AU - Almeida, Maria Camila

AU - Eger, Sarah J

AU - He, Caroline

AU - Audouard, Morgane

AU - Nikitina, Arina

AU - Glasauer, Stella M K

AU - Han, Dasol

AU - Mejía-Cupajita, Barbara

AU - Acosta-Uribe, Juliana

AU - Villalba-Moreno, Nelson David

AU - Littau, Jessica Lisa

AU - Elcheikhali, Megan

AU - Rivera, Erica Keane

AU - Carrettiero, Daniel Carneiro

AU - Villegas-Lanau, Carlos Andrés

AU - Sepulveda-Falla, Diego

AU - Lopera, Francisco

AU - Kosik, Kenneth S

N1 - Copyright © 2024 Elsevier Inc. All rights reserved.

PY - 2024/6/5

Y1 - 2024/6/5

N2 - Highly penetrant autosomal dominant Alzheimer's disease (ADAD) comprises a distinct disease entity as compared to the far more prevalent form of AD in which common variants collectively contribute to risk. The downstream pathways that distinguish these AD forms in specific cell types have not been deeply explored. We compared single-nucleus transcriptomes among a set of 27 cases divided among PSEN1-E280A ADAD carriers, sporadic AD, and controls. Autophagy genes and chaperones clearly defined the PSEN1-E280A cases compared to sporadic AD. Spatial transcriptomics validated the activation of chaperone-mediated autophagy genes in PSEN1-E280A. The PSEN1-E280A case in which much of the brain was spared neurofibrillary pathology and harbored a homozygous APOE3-Christchurch variant revealed possible explanations for protection from AD pathology including overexpression of LRP1 in astrocytes, increased expression of FKBP1B, and decreased PSEN1 expression in neurons. The unique cellular responses in ADAD and sporadic AD require consideration when designing clinical trials.

AB - Highly penetrant autosomal dominant Alzheimer's disease (ADAD) comprises a distinct disease entity as compared to the far more prevalent form of AD in which common variants collectively contribute to risk. The downstream pathways that distinguish these AD forms in specific cell types have not been deeply explored. We compared single-nucleus transcriptomes among a set of 27 cases divided among PSEN1-E280A ADAD carriers, sporadic AD, and controls. Autophagy genes and chaperones clearly defined the PSEN1-E280A cases compared to sporadic AD. Spatial transcriptomics validated the activation of chaperone-mediated autophagy genes in PSEN1-E280A. The PSEN1-E280A case in which much of the brain was spared neurofibrillary pathology and harbored a homozygous APOE3-Christchurch variant revealed possible explanations for protection from AD pathology including overexpression of LRP1 in astrocytes, increased expression of FKBP1B, and decreased PSEN1 expression in neurons. The unique cellular responses in ADAD and sporadic AD require consideration when designing clinical trials.

U2 - 10.1016/j.neuron.2024.02.009

DO - 10.1016/j.neuron.2024.02.009

M3 - SCORING: Journal article

C2 - 38417436

VL - 112

SP - 1778-1794.e7

JO - NEURON

JF - NEURON

SN - 0896-6273

IS - 11

ER -