our recent study revealed that prenatal exposure to bisphenol A (BpA) disrupted the transcriptome profiles of genes in the offspring hippocampus. In addition to genes linked to autism, several genes associated with Alzheimer's disease (AD) were found to be differentially expressed, although the association between BPA-responsive genes and AD-related genes has not been thoroughly investigated. Here, we demonstrated that in utero BpA exposure also disrupted the transcriptome profiles of genes associated with neuroinflammation and AD in the hippocampus. The level of NF-κB protein and its AD-related target gene Bace1 were significantly increased in the offspring hippocampus in a sex-dependent manner. Quantitative RT-PCR analysis also showed an increase in the expression of Tnf gene. Moreover, the reanalysis of transcriptome profiling data from several previously published BPA studies consistently showed that BPA-responsive genes were significantly associated with top AD candidate genes. The findings from this study suggest that maternal BPA exposure may increase AD risk in offspring by dysregulating genes associated with AD neuropathology and inflammation and reveal a possible relationship between AD and autism, which are linked to the same environmental factor. Sexspecific effects of prenatal BPA exposure on the susceptibility of AD deserve further investigation. Alzheimer's disease (AD) is the most common type of dementia and accounts for approximately 50-75% of dementia cases worldwide 1,2. AD is caused by progressive brain cell degeneration that affects wide areas of the cerebral cortices and hippocampi of patients, thus leading to various abnormalities, including memory loss, language difficulties, impaired decision making, and lack of other cognitive skills along with behavioral and emotional changes 3,4. Two major histological findings that are commonly found in the brain of AD patients are the (i) accumulation of extracellular amyloid plaques produced by abnormal aggregation of neurotoxic amyloid-β (Aβ) protein and (ii) intracellular neurofibrillary tangles (NFT) caused by hyperphosphorylation of tau 5,6. Amyloid plaque formation is often considered an upstream event in the pathogenesis of AD and is derived from the sequential cleavage of amyloid precursor protein (APP) by beta and gamma secretases 7. The beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), which is the key enzyme responsible for APP proteolysis, initiates the cleavage

Hyperglycemia is one of the important causes of neurodegenerative disorders and aging. Aquilaria crassna Pierre ex Lec (AC) has been widely used to relieve various health ailments. However, the neuroprotective and anti-aging effects against high glucose induction have not been investigated. This study aimed to investigate the effects of hexane extract of AC leaves (ACH) in vitro using human neuroblastoma SH-SY5Y cells and in vivo using nematode Caenorhabditis elegans. SH-SY5Y cells and C. elegans were pre-exposed with high glucose, followed by ACH treatment. To investigate neuroprotective activities, neurite outgrowth and cell cycle progression were determined in SH-SY5Y cells. In addition, C. elegans was used to determine ACH effects on antioxidant activity, longevity, and healthspan. In addition, ACH phytochemicals were analyzed and the possible active compounds were identified using a molecular docking study. ACH exerted neuroprotective effects by inducing neurite outgrowth via upregulating growth-associated protein 43 and teneurin-4 expression and normalizing cell cycle progression through the regulation of cyclin D1 and SIRT1 expression. Furthermore, ACH prolonged lifespan, improved body size, body length, and brood size, and reduced intracellular ROS accumulation in high glucose-induced C. elegans via the activation of gene expression in the DAF-16/FoxO pathway. Finally, phytochemicals of ACH were analyzed and revealed that β-sitosterol and stigmasterol were the possible active constituents in inhibiting insulin-like growth factor 1 receptor (IGFR). The results of this study establish ACH as an alternative medicine to defend against high glucose effects on neurotoxicity and aging.

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