Neuroinflammation in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.

Pathogenesis of Alzheimer’s disease: Involvement of the Choroid Plexus

“…We next investigated whether inflammatory changes in the CSF accompany the proinflammatory state of the ChP observed in AD. Considering that aging is the most important risk factor for AD and plays an equally important role in inflammation 29 , we first mined a well-established CSF dataset 30,31 for age-related changes. Mining showed abundant representation of inflammatory events among the top 20 most significantly changed pathways in the CSF by aging (Fig 2a).…”

“…preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted August 1, 2021. ; https://doi.org/10.1101/2021.07. 29.21260696 doi: medRxiv preprint groups (Supplementary Tbl. 4).…”

“…preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted August 1, 2021. ; https://doi.org/10.1101/2021.07. 29.21260696 doi: medRxiv preprint protein changes observed in AD. To investigate the involvement of the ChP in AD further, we stained ChP with anti-NPC2 and anti-APOE antibodies.…”

High-Fat and Resveratrol Supplemented Diets Modulate Adenosine Receptors in the Cerebral Cortex of C57BL/6J and SAMP8 Mice

“…All these data point out a potential role of 5′-NT-A 2A R signaling in the HFD-induced cognitive deterioration. Neuroinflammation is a key factor that may contribute to the progression of neurodegenerative disorders [ 73 , 74 , 75 ]. Microglial 5′-NT-A 2A R-mediated signaling modulates microglial immune-response in the brain [ 72 , 76 ], hence, this functional axis may represent a potential target to control neuroinflammation.…”

Successful and Unsuccessful Brain Aging in Pets: Pathophysiological Mechanisms behind Clinical Signs and Potential Benefits from Palmitoylethanolamide Nutritional Intervention

“…There is growing interest in understanding the role of neuroinflammation within the brain during both healthy and pathological aging [ 91 ]. Indeed, inflammatory processes have been found to be involved in the etiopathology of many neurological disorders.…”