Distinct transcriptomic responses to Aß plaques, neurofibrillary tangles, and APOE in Alzheimer's disease.
Alzheimers Dement
; 20(1): 74-90, 2024 Jan.
Article
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| MEDLINE
| ID: mdl-37461318
ABSTRACT
INTRODUCTION:
Omics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimer's disease (AD) but the spatial relationships with plaques and tangles and APOE-linked differences remain unclear.METHODS:
We performed laser capture microdissection of amyloid beta (Aß) plaques, the 50 µm halo around them, tangles with the 50 µm halo around them, and areas distant (> 50 µm) from plaques and tangles in the temporal cortex of AD and control donors, followed by RNA-sequencing.RESULTS:
Aß plaques exhibited upregulated microglial (neuroinflammation/phagocytosis) and downregulated neuronal (neurotransmission/energy metabolism) genes, whereas tangles had mostly downregulated neuronal genes. Aß plaques had more differentially expressed genes than tangles. We identified a gradient Aß plaque > peri-plaque > tangle > distant for these changes. AD APOE ε4 homozygotes had greater changes than APOE ε3 across locations, especially within Aß plaques.DISCUSSION:
Transcriptomic changes in AD consist primarily of neuroinflammation and neuronal dysfunction, are spatially associated mainly with Aß plaques, and are exacerbated by the APOE ε4 allele.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Revista:
Alzheimers Dement
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos