Knowledge, attitudes, and perspectives on gene therapy for Fragile X syndrome: results from two community and caregiver surveys.

Dementia represents a rapidly escalating global public health priority, with advancing age constituting the strongest non-modifiable risk factor. In 2021, the number of individuals living with dementia worldwide reached 57 million, of whom over 60% were in low- and middle-income countries; meanwhile, nearly 10 million new cases occur each year, making prevention and control increasingly urgent []. According to the World Health Organization (WHO), both the number and proportion of the global population aged 60 and over are continuously rising. In 2019, this cohort comprised approximately 1 billion individuals; it is projected to reach to 1.4 billion by 2030, and exceed 2.1 billion by 2050. This process of population aging is progressing at an unprecedented pace and will continue to accelerate in the coming decades, particularly in developing countries. The accelerating pace of population aging directly contributes to the escalating global prevalence of dementia. Alzheimer’s disease (AD) is the most prevalent dementia subtype; it exhibits epidemiological patterns that closely mirror those of dementia overall, thereby reinforcing its designation as a leading global health priority requiring urgent, rigorously evidence-based intervention. As a chronic progressive neurodegenerative disease, Alzheimer’s disease typically presents with memory loss as the initial symptom, follows a progressive course, and can ultimately lead to death. Its incidence increases significantly with age, making it one of the high-risk diseases that threaten human health []. Currently, no disease-modifying therapy exists for AD, and patients require long-term medication after diagnosis to delay disease progression, imposing a heavy disease burden on most countries and regions worldwide. Notably, women and the very elderly are at relatively higher risk and should be the key focus of clinical attention and prevention and control efforts. Against this backdrop, developing more effective prevention strategies and therapeutic interventions has become an urgent priority for reducing the disease burden of dementia []. AD brains exhibit show accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), along with neuroinflammation, synaptic dysfunction, mitochondrial and bioenergetic disturbances, and vascular abnormalities. Collectively, these processes can ultimately lead to neuronal death [,]. AD presents with a range of clinical symptoms; early-stage symptoms are predominantly amnestic, featuring prominent impairment in episodic memory and delayed recall. With the progression of AD, affected individuals may develop deficits in complex attention, expressive language, visuospatial abilities, and executive function []. Common AD comorbidities include dyslipidemia, hypertension, diabetes mellitus, obesity, depression, and cardiovascular disease. Complications arising from the progression of AD, such as thrombosis, mobility impairment, dysphagia, malnutrition, and pulmonary infection, can reduce patients’ quality of life and increase the risk of death [,,,,,]. Therefore, a large number of researchers have turned their attention to AD. A growing body of evidence indicates that immune processes play a key role in the pathogenesis of AD []. AD reflects systemic dysregulation of core aging processes: mitochondrial dysfunction, oxidative stress, neuroinflammation, ferroptosis, gut–brain axis disruption, and pathogen-associated molecular patterns. These mechanisms synergistically amplify Aβ and Tau pathology, driving progressive cognitive decline. Current clinical drugs can only alleviate symptoms and have safety limitations; therefore, there is an urgent clinical need for natural multi-target molecules that can simultaneously target aging and AD. In the past, lignans and their extracts have been reported to effectively protect neuronal cells and improve cognitive function []. Among the various classes of natural products, lignans, a group of polyphenolic dimers generated through oxidative coupling of two phenylpropanoid units has emerged as particularly interesting candidates. Earlier studies have shown that lignans and their crude extracts can protect neuronal cells and improve cognitive performance in experimental models []. Lignans align well with the demands of AD drug development. On the one hand, their moderate lipophilicity and relatively low molecular weight facilitate passage across the blood–brain barrier, a prerequisite for central nervous system activity. On the other hand, they display considerable structural variety, encompassing dibenzocyclooctadiene, tetrahydrofuran, bisepoxy, benzofuran, and biphenyl skeletons, which enables them to engage multiple AD-related targets, including Aβ aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, and mitochondrial dysfunction. In addition, many lignans are found in edible or medicinal plants and show favorable safety profiles, making them attractive for long-term