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Inflammation: The Missing Link Between Cardiometabolic, Immunologic, and Neurodegenerative Diseases

June 17, 2025 • 9-min read

Have you ever wondered why patients affected by obesity or other cardiometabolic conditions often suffer from a multitude of seemingly unrelated diseases, like psoriasis or Alzheimer’s disease? Recent research has uncovered commonalities within the pathologies behind these conditions that implicate chronic inflammation as a major driver of disease development and progression. This article summarizes the current research landscape of how inflammation is thought to contribute to the cooccurrence of seemingly unconnected diseases and their widespread impact on the global population.  

Inflammation is a transient evolutionary process whose role is to respond to injury or infection.1-4 However, under certain conditions, systemic, low-grade, chronic inflammation develops, resulting in damage to tissues or organs over time.1 Chronic inflammation has been implicated in a variety of cardiometabolic disorders such as type 2 diabetes, obesity, metabolic dysfunction–associated steatohepatitis (MASH), hypertension, and cardiovascular disease (CVD).1,4–8 Although the exact molecular mechanisms underlying chronic inflammation and the development of these disorders are yet to be fully elucidated,9 experts agree that inflammation can be both a cause and a consequence of various cardiometabolic diseases.3

Atherosclerosis (ACS), a chronic inflammatory disease associated with impaired metabolism, develops when low-density lipoprotein cholesterol accumulates in the endothelium of arteries, triggering an inflammatory response and plaque formation. Elevated circulating inflammatory markers such as C-reactive protein, serum amyloid A, interleukin (IL)-6, and IL-1 receptor antagonist commonly accompany ACS and independently correlate with in-hospital and short-term adverse prognoses.3,10-12

In type 2 diabetes, another cardiometabolic condition, elevated blood glucose induces oxidative stress that leads to chronic inflammation. This hyperglycemic state promotes the formation of advanced glycation end products, which bind to certain proteins and enhance the production of proinflammatory cytokines. Persistent inflammation results in insulin resistance that further exacerbates high glucose levels.3,11,13,14

In obesity, expanded adipose tissue releases cytokines and adipokines that promote a proinflammatory environment. Macrophage release of cytokines, tumor necrosis factor (TNF)-α, and IL-6 contributes to glucose disruptions and insulin resistance. Adipokine leptin participates in the regulation of innate and adaptive immune responses and elevates cytokine levels (Figure 1).3,7,11,15

Figure 1. Mechanisms of chronic inflammation in obesity.4,6,15–22

The inflammatory environments promoted by cardiometabolic diseases may increase risk or compound the severity of other conditions associated with chronic inflammation, as seen in some neurodegenerative and immunologic diseases.1 This interplay is seen in Alzheimer’s disease, a progressive neurodegenerative disorder that affects 27 million people worldwide and corresponds to 60%–70% of all dementia cases.23,24 Current research suggests that this neurodegenerative condition develops through the aggregation of amyloid β into fibrils, the formation of extracellular tangles by hyperphosphorylation of tau protein, and chronic neuroinflammation.15,19,24 The association between Alzheimer’s disease and inflammation-promoting cardiometabolic illnesses is corroborated by the observations that patients with obesity have an almost 2-fold higher risk of developing this disorder.25 Moreover, “type 3 diabetes” has been suggested as a name for Alzheimer’s disease because of its link to type 2 diabetes.19

Psoriasis is a chronic, inflammatory disease that affects 125 million people globally.9 This autoimmune disorder, along with other skin diseases such as atopic dermatitis and hidradenitis suppurativa, are associated with the occurrence of obesity, and their risk increases with high abdominal fat as well as weight gain.26–33 Psoriasis has also been linked to other inflammatory cardiometabolic disorders such as type 2 diabetes and CVD.26,34,35 The pathophysiology of this autoimmune disease includes stimulation of immune cells, leading to increased generation of proinflammatory cytokines and immune-modulating activity of adipokines.26,31,34

Atopic dermatitis, also known as atopic eczema, is a chronic, recurrent, inflammatory disease that affects 171 million individuals worldwide.20,36–38 The pathophysiology of atopic dermatitis is multifactorial and involves skin barrier impairment through cytokine-stimulated immune response.38 As with psoriasis, research on atopic dermatitis has demonstrated associations with cardiovascular and metabolic diseases.39 Together, the cardiometabolic, neurodegenerative, and immunologic diseases discussed above affect millions of people globally (Figure 2). Therefore, it is crucial to expand our understanding of the components and intricate mechanisms involved in the generation of these conditions.

Figure 2. Global impact of diseases linked to chronic inflammation.9,24,29,37,40–42

Chronic inflammation appears to be a connection shared by multiple cardiometabolic, neurodegenerative, and immunologic disorders. Evolving insights into the role of inflammation in pathophysiology across disease states have opened important new areas of clinical research, including the potential to use inflammatory biomarkers for disease risk stratification and monitoring treatment response.11 Because it is possible that there are joint pathophysiological mechanisms underlying these conditions, therapies that target shared inflammatory pathways may be beneficial to patients.

In our next article, we will focus on rapidly evolving novel treatment options – ie, incretins – that are poised to become a potential solution for targeting systemic diseases connected by common, yet not fully understood, molecular pathways.

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