阿尔茨海默病的多组学研究进展

doi:10.3969/j.issn.1003-9198.2025.10.007

Abstract

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and neuronal damage, with its pathogenesis involving the interaction of multiple factors including genetic, epigenetic, proteostatic imbalance, and metabolic disorders. In recent years, integrated studies using multi-omics technologies such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics provide new insights into AD’s molecular mechanisms. The integration of multi-omics data not only aids in discovering early biomarkers for AD but also offers novel strategies for targeted therapies (such as HDAC6 inhibitors and natural compound interventions). Future research should combine single-cell technology with artificial intelligence to advance precision diagnosis and treatment of AD.

Key words: Alzheimer’s disease, multi-omics research, advance

CLC Number:

R 749.16

YUAN Lili, ZOU Qiangwei. Advances in multi-omics research on Alzheimer’s disease[J]. Practical Geriatrics, 2025, 39(10): 1003-1008.

References

[1] BREIJYEH Z, KARAMAN R. Comprehensive review on Alzheimer’s disease: causes and treatment[J]. Molecules, 2020, 25(24):5789.
[2] HANG X X, TIAN Y, WANG Z T,et al. The epidemiology of Alzheimer’s disease modifiable risk factors and prevention[J]. J Prev Alzheimers Dis,2021,8(3):313-321.
[3] YAMAZAKI Y, ZHAO N, CAULFIELD T R, et al. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies[J]. Nat Rev Neurol, 2019, 15(9):501-518.
[4] JUNG J H, JEON S, BAIK K, et al Apolipoprotein E4, amyloid, and cognition in Alzheimer’s and Lewy body disease[J]. Neurobiol Aging, 2021, 106:45-54.
[5] YIN Y, YANG H, LI R, et al. A systematic review of the role of TREM2 in Alzheimer’s disease.[J]. Chin Med J: Engl, 2024, 137(14):1684-1694.
[6] LOY C T, SCHOFIELD P R, TURNER A M, et al. Genetics of dementia.[J] Lancet, 2024, 383(9919):828-840.
[7] APOSTOLOVA L G, RISACHER S L, DURAN T, et al. Associations of the top 20 Alzheimer disease risk variants with brain amyloidosis[J]. JAMA Neurol, 2018, 75(3): 328-341.
[8] KIM J P, JUNG S H, JANG B, et al. Cross-ancestry genome-wide association study identifies implications of SORL1 in cerebral beta-amyloid deposition[J]. Nat Commun, 2025, 16(1): 3150.
[9] ASADIFARD E, HOKMABADI M, HASHEMI M, et al. Linking gut microbiota dysbiosis to molecular pathways in Alzheimer’s disease[J]. Brain Res, 2024, 1845: 149242.
[10] 汤雅宁, 吉丽娜, 华子春. 基于大数据分析探究影响阿尔兹海默症疾病进展的关键基因及通路[J]. 药物生物技术, 2022, 29(4): 331-337.
[11] STRATH L J, MENG L, ZHANG Y, et al. Differential DNA methylation profiles of Alzheimer’s disease-related genomic pathways in the blood of cognitively-intact individuals with and without high impact chronic pain[J]. J Alzheimers Dis Rep, 2024, 8(1): 1549-1557.
[12] SAVELEVA L, CERVENA T, MENGONI C, et al. Transcriptomic and epigenomic profiling reveals altered responses to diesel emissions in Alzheimer’s disease both in vitro and in population-based data[J]. Alzheimers Dement, 2024, 20(12): 8825-8843.
[13] GOLD A, KAYE S, GAO J, et al. Propionate decreases microglial activation but impairs phagocytic capacity in response to aggregated fibrillar amyloid beta protein[J]. ACS Chem Neurosci, 2024, 15(21): 4010-4020.
[14] CHINNATHAMBI S. Histone deacetylase’s regulates Tau function in Alzheimer’s disease[J]. Adv Protein Chem Struct Biol, 2025, 143: 339-361.
[15] LIU Q, WANG X, FANG Z T, et al. Upregulation of ISG15 induced by MAPT/tau accumulation represses autophagic flux by inhibiting HDAC6 activity: a vicious cycle in Alzheimer disease[J]. Autophagy, 2025, 21(4): 807-826.
[16] GRAVES P, ZENG Y. Biogenesis of mammalian microRNAs: a global view[J]. Genomics Proteomics Bioinformatics, 2012, 10(5): 239-245.
[17] SUN Y, PANG X, HUANG X, et al.Potential mechanisms of non-coding RNA regulation in Alzheimer’s disease[J].Neural Regen Res, 2026, 21(1):265-280. doi: 10.4103/NRR.NRR-D-24-00696.
[18] KIKUCHI M, SEKIYA M, HARA N,et al. The disruption of the network centered on RAC1 is associated with the pathology of Alzheimer’s disease and leads to age-dependent neurodegeration[J]. Human Mol gene, 2020, 29: 817-833.
[19] FENG Y, YU X, HAN J. Quercetin regulates the polarization of microglia through the NRF2/HO1 pathway and mitigates Alzheimer’s disease[J]. Actas Esp Psiquiatr, 2024, 52(6): 786-799.
[20] LÓPEZ-CEPEDA M L, ANGARITA-RODRÍGUEZ A, ROJAS-CRUZ A F, et al. Extracellular competing endogenous RNA networks reveal key regulators of early amyloid pathology propagation in Alzheimer’s disease[J].Int J Mol Sci,2025,26(8):3544.
[21] IGA J I, YOSHINO Y, OZAKI T, et al. Blood RNA transcripts show changes in inflammation and lipid metabolism in Alzheimer’s disease and mitochondrial function in mild cognitive impairment[J]. J Alzheimers Dis Rep, 2024, 8(1): 1690-1703.
[22] ITSUNO M, TANABE H, SANO E, et al.MAPT-A152T mutation drives neuronal hyperactivity through Fyn-NMDAR signaling in human iPSC-Derived neurons: insights into Alzheimer’s pathogenesis[J].Regen Ther,2025,28:201-213.
[23] BEYDOUN M A, BEYDOUN H A, LI Z, et al. Alzheimer’s disease polygenic risk, the plasma proteome, and dementia incidence among UK older adults[J]. Geroscience, 2025, 47(2): 2507-2523.
[24] 李明希, 张桂美, 尚天玲, 等. Aβ诱导依赖caspase-1/GSDMD通路的细胞焦亡与阿尔兹海默病的研究进展[J]. 中国免疫学杂志, 2021, 37(24): 3070-3074.
[25] PHILIPPI S M, BP K, RAJ T, et al. APOE genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia[J]. Ann Clin Transl Neurol, 2025, 12(2): 366-382.
[26] SUN Y, BAI G, YANG K, et.al.Multi-target neuroprotection by dl-PHPB in APP/PS1 mice: a proteomic analysis[J].Front Pharmacol, 2025, 16: 1554168.
[27] FU J, LIANG Z, CHEN Z, et al. Deciphering the therapeutic efficacy and underlying mechanisms of dendrobium officinale polysaccharides in the intervention of Alzheimer’s disease mice: insights from metabolomics and microbiome[J]. J Agric Food Chem, 2025, 73(9): 5635-5648.
[28] SHUKLA A, MEENA K, GUPTA A, et al. 1H NMR-based metabolomic signatures in rodent models of sporadic Alzheimer’s disease and metabolic disorders[J]. ACS Chem Neurosci, 2024, 15(24): 4478-4499.
[29] MATTHEWS D G, KHORANI M, BOBE G, et al. Centella asiatica improves cognitive function and alters the hippocampal metabolome of aged Tg2576 and wild-type mice[J]. J Alzheimers Dis Rep, 2024, 8(1): 1611-1638.
[30] LIU J, ZHANG Y, ZHANG M, et al. 6'''-Feruloylspinosin alleviates Aβ-induced toxicity by modulating relevant neurotransmitter and the AMPK/mTOR signaling pathway[J]. Free Radic Biol Med, 2025, 227: 434-445.
[31] LI H, HUANG J, ZHAO D, et al. Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease[J]. Neural Regen Res, 2025, 20(10): 2982-2997.
[32] MIR M, KHOSRAVANI P, RAMEZANNEZHAD E, et al. Associations between metabolomics findings and brain hypometabolism in mild cognitive impairment and Alzheimer’s disease[J]. Curr Alzheimer Res, 2024, 21(9): 679-689.
[33] FRANÇOIS M, PASCOVICI D, WANG Y, et al. Saliva proteome, metabolome and microbiome signatures for detection of Alzheimer’s disease[J]. Metabolites, 2024, 14(12): 714.
[34] İŞ Ö, MIN Y, WANG X, et al. Multi layered omics approaches reveal Glia specific alterations in Alzheimer’s disease: a systematic review and future prospects[J]. Glia, 2025, 73(3): 539-573.
[35] PENG D, LIU T, LU H, et al. Intranasal delivery of engineered extracellular vesicles loaded with miR-206-3p antagomir ameliorates Alzheimer’s disease phenotypes[J]. Theranostics, 2024, 14(19): 7623-7644.
[36] LIN M, ZHOU Y, LIANG P, et al. Identification of Alzheimer’s disease biomarkers and their immune function characterization[J]. Arch Med Sci, 2025, 21(1):233-257.
[37] JIANG J, ZHAO K, LI W, et al. Multiomics reveals biological mechanisms linking macroscale structural covariance network dysfunction with neuropsychiatric symptoms across the Alzheimer’s disease continuum[J]. Biol Psychiatry, 2025, 97(11): 1067-1078.

Advances in multi-omics research on Alzheimer’s disease

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Metrics

Recommended 10

[1]	WANG Miaohui, FAN Xuhang, CHEN Siyao, YANG Xiaojuan. Research progress on the correlation between Alzheimer’s disease and osteoporosis [J]. Practical Geriatrics, 2025, 39(9): 937-941.
[2]	YANG Huijuan, LIU Shunying, SU Jing, ZENG Liting. Advances in the application of artificial intelligence in the full-course management of Alzheimer’s disease [J]. Practical Geriatrics, 2025, 39(8): 768-772.
[3]	ZHONG Yi, FENG Yue, ZHANG Xinlong, DING Rui, SI Yanna. Research progress in single-cell RNA sequencing for Alzheimer’s disease [J]. Practical Geriatrics, 2025, 39(8): 857-861.
[4]	GU Xingyue, GAO Wei, LU Xiang. Advances in the study of enzymatic protein glycosylation in Alzheimer’s disease [J]. Practical Geriatrics, 2025, 39(6): 631-635.
[5]	WANG Yun, FU Liping. Significance of retinal structural and functional changes in the diagnosis of Alzheimer’s disease in high-altitude regions [J]. Practical Geriatrics, 2025, 39(5): 461-465.
[6]	WANG Yan, XU Jie, GU Xiaoping. Research advances on association between fatty acid metabolism and Alzheimer’s disease [J]. Practical Geriatrics, 2025, 39(4): 415-419.
[7]	LIN Xiaoqi, ZHAO Xinjing, WU Yashuang, ZHAO Wei, CHEN Chen, GAO Tianyu, ZHOU Guoyu. Advances of the mechanisms of gender differences in Alzheimer’s disease [J]. Practical Geriatrics, 2025, 39(4): 420-425.
[8]	ZHANG Kongyan. Advances in multi-omics research on depression in the elderly [J]. Practical Geriatrics, 2025, 39(10): 976-981.
[9]	ZHANG Fei, WANG Ziwen, WANG Jinyun, WU Dishan, WANG Zhong. Advances in multi-omics research on frailty [J]. Practical Geriatrics, 2025, 39(10): 982-986.
[10]	HU Xinyi, LI Dingkun, Aeryoubu, DUAN Jingyi, LIAO Xichu, GAO Haiying. Advances in multi-omics research on sleep disorders in elderly [J]. Practical Geriatrics, 2025, 39(10): 987-991.
[11]	HUANG Rui. Prediction value of GNRI and CONUT score for≥grade 2 radiation pneumonia after radiotherapy in elderly patients with locally advanced non-small cell lung cancer [J]. Practical Geriatrics, 2024, 38(8): 831-836.
[12]	LI Qingyang, WANG Chanjuan, WANG Zheng. Study on the correlation of cognitive function with swallowing function and nutritional status in the elderly patients with Alzheimer’s disease [J]. Practical Geriatrics, 2024, 38(6): 577-581.
[13]	LIU Tian, YANG Rongli, HAN Huiping. Value of serum levels of Aβ1-42 and Bcl-2 in predicting the pathogenesis of Alzheimer’s disease in elderly patients with cognitive impairment [J]. Practical Geriatrics, 2024, 38(6): 582-586.
[14]	WANG Bingsheng, CAO Shihua, CHENG Lingling, SHI Aili, SHI Yankai, YAO Jiani, LOU Xiajing, QI Wenhao, DONG Chaoqun, ZHU Xiaohong, WANG Bing, HE Danni, CHEN Yanfei. A nomogram prediction model for risk of Alzheimer’s disease among the elderly [J]. Practical Geriatrics, 2024, 38(12): 1246-1249.
[15]	LIU Li-juan, JIANG Man, CHENG Yong, MAO Gao-feng, FANG Huang. Relationship of serum levels of AGEs and RAGE with dementia severity in elderly patients with vascular dementia after cerebral infarction [J]. Practical Geriatrics, 2023, 37(8): 853-857.