Abstract

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid plaques, tau-containing neurofibrillary tangles and cognitive decline. Emerging evidence suggests that chronic neuroinflammation, disrupted Cyclic Adenosine Mono Phosphate (cAMP) signaling and early olfactory dysfunction accelerate disease progression. Phosphodiesterase-4 (PDE4) inhibitors, such as roflumilast, enhance cAMP-mediated signaling and exhibit anti-inflammatory and neuroprotective effects. Complementary interventions-including flavonoids, lignans and vitamin D-may modulate the brain-lung-olfactory axis and further mitigate neuroinflammation. This review proposes an integrated pharmacological and nutritional strategy targeting systemic and central inflammatory pathways, offering a novel framework for preventive and therapeutic approaches in AD.

Keywords: Alzheimer’s disease; Phosphodiesterase-4 (PDE4) inhibitors; Roflumilast; Neuroinflammation; cAMP signaling; CREB pathway; Olfactory dysfunction; Tau protein; β-amyloid; Flavonoids; Lignans; Vitamin D; Brain-lung axis; Cognitive decline; Neuroprotection