Neuronal driven pre-plaque inflammation in a transgenic rat model of Alzheimer's disease.
Chronic brain inflammation is associated with Alzheimer's disease (AD) and is classically attributed to amyloid plaque deposition. However, whether the amyloid pathology can trigger early inflammatory processes before plaque deposition remains a matter of debate. To address the possibility that a pre-plaque inflammatory process occurs, we investigated the status of neuronal, astrocytic, and microglial markers in pre- and post-amyloid plaque stages in a novel transgenic rat model of an AD-like amyloid pathology (McGill-R-Thy1-APP). In this model, we found a marked upregulation of several classical inflammatory markers such as COX-2, IL-1β, TNF-α, and fractalkine (CX3CL1) in the cerebral cortex and hippocampus. Interestingly, many of these markers were highly expressed in amyloid beta-burdened neurons. Activated astrocytes and microglia were associated with these Aβ-burdened neurons. These findings confirm the occurrence of a proinflammatory process preceding amyloid plaque deposition and suggest that Aβ-burdened neurons play a crucial role in initiating inflammation in AD.
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Cecilia E
CE
Hanzel
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Alexa
A
Pichet-Binette
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Luisa S B
LS
Pimentel
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
M Florencia
MF
Iulita
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Simon
S
Allard
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Adriana
A
Ducatenzeiler
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Sonia
S
Do Carmo
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. Electronic address: claudio.cuello@mcgill.ca.
A Claudio
AC
Cuello
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology*; D055647:Rats, Transgenic
D016229:Amyloid beta-Peptides
Alzheimer's disease; Astrocytosis; Aβ-burdened neurons; Inflammation; Microgliosis; Pre-plaque; Transgenic animal models