Abstract: Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by a loss of cognitive function, behavioral changes, and neurodegeneration. The occurrence of Aβ plaques in the brain and the formation of neurofibrillary tangles (NFTs) are hallmarks of the disease. Neuroinflammation and glycoprotein metabolism, particularly neuraminidase 1 (NEU1), are emerging as crucial factors in AD pathogenesis and remain underexplored. This review aims to identify the role of NEU1 in AD pathogenesis and its potential as a therapeutic target. Studies published between 2017 and 2024 were included, focusing on AD, dementia, pathology, the amyloid hypothesis, treatment, neuraminidase, and neuraminidase modulators using PubMed, Google Scholar, Scopus, EMBASE, and other databases. To address the underlying pathophysiology of AD, several therapeutic strategies target key proteins and enzymes involved in Aβ and tau aggregation, as well as neurotransmitter signalling. Inhibitors of cholinesterase are currently approved for symptomatic treatment. However, these medications only provide modest relief and do not modify disease progression. Emerging evidence demonstrated that NEU1 deficiency leads to the accumulation of amyloid precursor protein (APP) and Aβ precursor. This accumulation disrupts lysosomal function and autophagy, exacerbating Aβ and tau pathology. Modulating NEU1 activity by developing specific activators offers a promising therapeutic approach for AD. Such compounds could reduce Aβ production, enhance Aβ clearance, and alleviate neuroinflammation. In conclusion, targeting NEU1 represents a promising avenue for AD therapies. Further study is necessary to elucidate the precise mechanisms for NEU1's contribution to AD and to elucidate effective NEU1-based interventions.
Alzarea et al. (2026) studied this question.