Adipose tissue as a therapeutic target for vascular damage in Alzheimer's disease

Abstract

The adipose tissue (AT) has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in multiple metabolic tissues. With this regard, emerging evidence indicates that an important crosstalk exists between the AT and the brain. However, the AT contribution in the development of age‐related diseases, including Alzheimer’s disease (AD), remains poorly defined. New studies suggest that the AT modulates brain function through multiple bioactive factors known as adipokines, which can cross the blood brain barrier (BBB) to reach the brain target‐areas or even regulate the BBB function. In this review, we discuss the effect of multiple adipokines in the BBB physiology, their contribution to the development of AD and their therapeutic potential.

Impaired Remodeling of White Adipose Tissue in Obesity and Aging: From Defective Adipogenesis to Adipose Organ Dysfunction

“…In particular, a great deal of research indicates that AT influences brain function via adipokines, which can cross the blood-brain barrier to affect target areas or regulate its function. Adipokines play a significant role in various brain functions, including synaptic plasticity, memory formation, neurogenesis, inflammatory responses, and the maintenance of the blood-brain barrier [269]. Consistently, obesity, T2DM, and other metabolic disorders associated with altered adipokine production increase the risk of cognitive impairment and numerous neurodegenerative diseases, including AD [270][271][272][273].…”

“…The role of adipokines in regulating adipose-brain cross-talk and the associated risk of developing cognitive decline and dementia has recently been comprehensively reviewed [269]. However, adipokines are not the sole adipose factor capable of regulating the brain.…”

Neuro-Adipokine Crosstalk in Alzheimer’s Disease

“…It is unlikely that the manipulation of a single adipokine will have a pronounced effect on the brain; rather, the focus should be on achieving a healthy adipose tissue environment, leading to a proper balance of overall adipokine levels. Targeting the adipose tissue to repair vascular damage in AD and other neurological disorders is a novel approach that changes the landscape of viewing and treating CNS disorders [ 115 ]. Furthermore, the effects of metabolic treatment on AD should expand from canonical AD pathologies such as amyloid plaques and neurofibrillary tangles to the neuro–glial–vascular landscape encompassing the neurovascular unit, blood-brain barrier, myelin sheath, and glymphatic drainage [ 116 ].…”