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Review
. 2024 Dec;28(23):e70118.
doi: 10.1111/jcmm.70118.

New insight on the potential detrimental effect of metabolic syndrome on the Alzheimer disease neuropathology: Mechanistic role

Naif H Ali  1 , Hayder M Al-Kuraishy  2 , Ali I Al-Gareeb  3 , Athanasios Alexiou  4   5   6   7 , Marios Papadakis  8 , Mostafa M Bahaa  9 , Fawaz Alibrahim  10 , Gaber El-Saber Batiha  11
Affiliations
Review

New insight on the potential detrimental effect of metabolic syndrome on the Alzheimer disease neuropathology: Mechanistic role

Naif H Ali et al. J Cell Mol Med. 2024 Dec.

Abstract

The metabolic syndrome or syndrome X is a clustering of different components counting insulin resistance (IR), glucose intolerance, visceral obesity, hypertension and dyslipidemia. It has been shown that IR and dysregulation of insulin signalling play a critical role in the development of metabolic syndrome by initiating the pathophysiology of metabolic syndrome through induction of glucolipotoxicity, impairment of glucose disposal and triggering of pro-inflammatory response. Furthermore, metabolic syndrome unfavourably affects the cognitive function and the development of different neurodegenerative diseases such as Alzheimer disease (AD) by inducing oxidative stress, neuroinflammation and brain IR. These changes together with brain IR impair cerebrovascular reactivity leading to cognitive impairment. In addition, metabolic syndrome increases the risk for the development of AD. However, the central mechanisms by which metabolic syndrome amplify AD risk are not completely elucidated. Consequently, this narrative review aims to revise from published articles the association between metabolic syndrome and AD regarding cellular and subcellular pathways. In conclusion, metabolic syndrome is regarded as a potential risk factor for the induction of AD neuropathology by different signalling pathways such as initiation of brain IR, activation of inflammatory signalling pathways and neuroinflammation.

Keywords: Alzheimer disease; metabolic syndrome; neuroinflammation.

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Conflict of interest statement

The authors declare no competing interests.

Figures

FIGURE 1
FIGURE 1
The potential role visceral adiposity in the development of metabolic syndrome.
FIGURE 2
FIGURE 2
Pathogenesis of Alzheimer's disease (AD).
FIGURE 3
FIGURE 3
Brain insulin resistance (IR) and Alzheimer disease (AD) neuropathology.
FIGURE 4
FIGURE 4
Metabolic syndrome and risk of brain insulin resistance (IR).
FIGURE 5
FIGURE 5
GSK3β overactivity and Alzheimer disease (AD) neuropathology.
See this image and copyright information in PMC

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