Cognitive and brain cytokine profile of non-demented individuals with cerebral amyloid-beta deposition

• Main Authors: Lisi Flores-Aguilar, M. Florencia Iulita, Chiara Orciani, Neil Tanna, Jingyun Yang, David A. Bennett, A. Claudio Cuello
• Format: Article
• Language: English
• Published: BMC 2021-07-01
• Series: Journal of Neuroinflammation
• Subjects: Amyloid-beta; Cognition; Cytokines; Alzheimer’s disease; Neuroinflammation; Perceptual speed
• Online Access: https://doi.org/10.1186/s12974-021-02169-0

Abstract Background Brain inflammation has been increasingly associated with early amyloid accumulation in Alzheimer’s disease models; however, evidence of its occurrence in humans remains scarce. To elucidate whether amyloid deposition is associated with neuroinflammation and cognitive deficits, we studied brain inflammatory cytokine expression and cognitive decline in non-demented elderly individuals with and without cerebral amyloid-beta deposition. Methods Global cognition, episodic, working, and semantic memory, perceptual speed, visuospatial ability, and longitudinal decline (5.7 ± 3.6 years) in each cognitive domain were compared between elderly individuals (66–79 years) with and without cerebral amyloid-beta deposition. The expression of 20 inflammatory cytokines was analyzed in frozen temporal, parietal, and frontal cortices and compared between older individuals with and without amyloid-beta deposition in each brain region. Correlation analyses were performed to analyze associations between amyloid-beta load, cytokine expression, and cognitive decline. Results Individuals with cortical amyloid-beta deposition displayed deficits and a faster rate of cognitive decline in perceptual speed as compared with those individuals without amyloid-beta. This decline was positively associated with cortical amyloid-beta levels. Elderly individuals with amyloid-beta deposition had higher levels of IL-1β, IL-6, and eotaxin-3 in the temporal cortex accompanied by an increase in MCP-1 and IL-1β in the parietal cortex and a trend towards higher levels of IL-1β and MCP-1 in the frontal cortex as compared with age-matched amyloid-free individuals. Brain IL-1β levels displayed a positive association with cortical amyloid burden in each brain region. Finally, differential cytokine expression in each cortical region was associated with cognitive decline. Conclusions Elderly individuals with amyloid-beta neuropathology but no symptomatic manifestation of dementia, exhibit cognitive decline and increased brain cytokine expression. Such observations suggest that increased cytokine expression might be an early event in the Alzheimer’s continuum.