Alzheimer’s disease as a public health and clinical challenge: risk factors, biomarkers, and treatment strategies
DOI:
https://doi.org/10.12775/JEHS.2026.92.72503Keywords
Alzheimer’s Disease, biomarkers, amyloid-β, tauAbstract
Introduction and purpose: Alzheimer’s disease (AD) is the most common cause of dementia and a growing clinical and public health challenge in ageing populations. Its rising prevalence, high social and economic burden, and lack of curative therapy highlight the need for better understanding of its mechanisms, risk factors, diagnostic tools, and treatment strategies. This review summarizes current knowledge on AD, with particular emphasis on biomarkers, modifiable risk factors, and emerging therapeutic approaches.
Brief description of the state of knowledge: AD is characterized by extracellular amyloid-β deposition and intracellular accumulation of hyperphosphorylated tau; however, its pathogenesis is multifactorial and also involves neuroinflammation, gliosis, mitochondrial dysfunction, neuronal loss, demyelination, and genetic susceptibility. Age is the strongest risk factor, while low educational attainment, physical inactivity, obesity, cardiovascular risk factors, depression, hearing loss, and social isolation may also increase disease risk. Biomarkers, including amyloid PET, tau PET, cerebrospinal fluid analytes, and blood-based markers such as phosphorylated tau, neurofilament light chain, and glial fibrillary acidic protein, improve early and accurate diagnosis. Current treatment is mainly symptomatic, but anti-amyloid, anti-tau, immunological, and non-pharmacological strategies are under intensive investigation.
Summary: Alzheimer’s disease should be viewed as both a neurodegenerative disorder and a public health challenge requiring prevention, early diagnosis, risk reduction, and personalized management. Further advances in biomarkers and targeted therapies may improve diagnostic precision and support more effective care.
References
1. Vermunt L, Sikkes SAM, van den Hout A, et al. Duration of Preclinical, Prodromal and Dementia Alzheimer Disease Stages in Relation to Age, Sex, and APOE genotype. Alzheimers Dement J Alzheimers Assoc. 2019;15(7):888-898. https://doi.org/10.1016/j.jalz.2019.04.001
2. Fakhoury M. Inflammation in Alzheimer’s Disease. Curr Alzheimer Res. 2020;17(11):959-961. https://doi.org/10.2174/156720501711210101110513
3. Twarowski B, Herbet M. Inflammatory Processes in Alzheimer’s Disease-Pathomechanism, Diagnosis and Treatment: A Review. Int J Mol Sci. 2023;24(7):6518. https://doi.org/10.3390/ijms24076518
4. D’Alessandro MCB, Kanaan S, Geller M, Praticò D, Daher JPL. Mitochondrial dysfunction in Alzheimer’s disease. Ageing Res Rev. 2025;107:102713. https://doi.org/10.1016/j.arr.2025.102713
5. Wang C, Zong S, Cui X, et al. The effects of microglia-associated neuroinflammation on Alzheimer’s disease. Front Immunol. 2023;14:1117172. https://doi.org/10.3389/fimmu.2023.1117172
6. Mothes T, Portal B, Konstantinidis E, et al. Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology. Acta Neuropathol Commun. 2023;11:97. https://doi.org/10.1186/s40478-023-01589-8
7. Dias D, Portugal CC, Relvas J, Socodato R. From Genetics to Neuroinflammation: The Impact of ApoE4 on Microglial Function in Alzheimer’s Disease. Cells. 2025;14(4):243. https://doi.org/10.3390/cells14040243
8. Dementia. Accessed April 17, 2025. https://www.who.int/news-room/fact-sheets/detail/dementia
9. Cao Q, Tan CC, Xu W, et al. The Prevalence of Dementia: A Systematic Review and Meta-Analysis. J Alzheimers Dis JAD. 2020;73(3):1157-1166. https://doi.org/10.3233/JAD-191092
10. Chen C, Zissimopoulos JM. Racial and ethnic differences in trends in dementia prevalence and risk factors in the United States. Alzheimers Dement N Y N. 2018;4:510-520. https://doi.org/10.1016/j.trci.2018.08.009
11. Genin E, Hannequin D, Wallon D, et al. APOE AND ALZHEIMER DISEASE: A MAJOR GENE WITH SEMI-DOMINANT INHERITANCE. Mol Psychiatry. 2011;16(9):903-907. https://doi.org/10.1038/mp.2011.52
12. Early-Onset Alzheimer’s Disease: What Is Missing in Research? - PMC. Accessed April 17, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC7815616/
13. Bellenguez C, Küçükali F, Jansen IE, et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet. 2022;54(4):412-436. https://doi.org/10.1038/s41588-022-01024-z
14. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet Lond Engl. 2020;396(10248):413-446. https://doi.org/10.1016/S0140-6736(20)30367-6
15. Atri A. The Alzheimer’s Disease Clinical Spectrum: Diagnosis and Management. Med Clin North Am. 2019;103(2):263-293. https://doi.org/10.1016/j.mcna.2018.10.009
16. Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: Mild cognitive impairment. Neurology. 2018;90(3):126-135. https://doi.org/10.1212/WNL.0000000000004826
17. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc. 2011;7(3):263-269. https://doi.org/10.1016/j.jalz.2011.03.005
18. Jack Jr. CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimers Dement. 2024;20(8):5143-5169. https://doi.org/10.1002/alz.13859
19. Savva GM, Wharton SB, Ince PG, et al. Age, neuropathology, and dementia. N Engl J Med. 2009;360(22):2302-2309. https://doi.org/10.1056/NEJMoa0806142
20. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985;82(12):4245-4249. Accessed April 21, 2025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC397973/
21. Dyrks T, Weidemann A, Multhaup G, et al. Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer’s disease. EMBO J. 1988;7(4):949-957. Accessed April 22, 2025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC454420/
22. Landes SD, Stevens JD, Turk MA. Cause of Death in Adults with Down Syndrome in the US. Disabil Health J. 2020;13(4):100947. https://doi.org/10.1016/j.dhjo.2020.100947
23. McCarron M, McCallion P, Reilly E, Dunne P, Carroll R, Mulryan N. A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome. J Intellect Disabil Res JIDR. 2017;61(9):843-852. https://doi.org/10.1111/jir.12390
24. Englund A, Jonsson B, Zander CS, Gustafsson J, Annerén G. Changes in mortality and causes of death in the Swedish Down syndrome population. Am J Med Genet A. 2013;161A(4):642-649. https://doi.org/10.1002/ajmg.a.35706
25. Soba P, Eggert S, Wagner K, et al. Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J. 2005;24(20):3624-3634. https://doi.org/10.1038/sj.emboj.7600824
26. Obregon D, Hou H, Deng J, et al. sAPP-α modulates β-secretase activity and amyloid-β generation. Nat Commun. 2012;3:777. https://doi.org/10.1038/ncomms1781
27. Laird FM, Cai H, Savonenko AV, et al. BACE1, a Major Determinant of Selective Vulnerability of the Brain to Amyloid-β Amyloidogenesis, is Essential for Cognitive, Emotional, and Synaptic Functions. J Neurosci. 2005;25(50):11693-11709. https://doi.org/10.1523/JNEUROSCI.2766-05.2005
28. Andrew RJ, Fernandez CG, Stanley M, et al. Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer’s disease. Proc Natl Acad Sci U S A. 2017;114(45):E9665-E9674. https://doi.org/10.1073/pnas.1708568114
29. De Strooper B. Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron. 2003;38(1):9-12. https://doi.org/10.1016/s0896-6273(03)00205-8
30. Gu L, Liu C, Guo Z. Structural Insights into Aβ42 Oligomers Using Site-directed Spin Labeling♦. J Biol Chem. 2013;288(26):18673-18683. https://doi.org/10.1074/jbc.M113.457739
31. Willem M, Tahirovic S, Busche MA, et al. η-Secretase processing of APP inhibits neuronal activity in the hippocampus. Nature. 2015;526(7573):443-447. https://doi.org/10.1038/nature14864
32. Park SA, Shaked GM, Bredesen DE, Koo EH. Mechanism of cytotoxicity mediated by the C31 fragment of the Amyloid Precursor Protein. Biochem Biophys Res Commun. 2009;388(2):450-455. https://doi.org/10.1016/j.bbrc.2009.08.042
33. Yang T, Li S, Xu H, Walsh DM, Selkoe DJ. Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate. J Neurosci. 2017;37(1):152-163. https://doi.org/10.1523/JNEUROSCI.1698-16.2016
34. Walker LC, Jucker M. Neurodegenerative Diseases: Expanding the Prion Concept. Annu Rev Neurosci. 2015;38:87-103. https://doi.org/10.1146/annurev-neuro-071714-033828
35. Purro SA, Farrow MA, Linehan J, et al. Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone. Nature. 2018;564(7736):415-419. https://doi.org/10.1038/s41586-018-0790-y
36. Abelein A. Metal Binding of Alzheimer’s Amyloid-β and Its Effect on Peptide Self-Assembly. Acc Chem Res. 2023;56(19):2653-2663. https://doi.org/10.1021/acs.accounts.3c00370
37. Iannuzzi C, Irace G, Sirangelo I. The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity. Molecules. 2015;20(2):2510-2528. https://doi.org/10.3390/molecules20022510
38. Garai K, Verghese PB, Baban B, Holtzman DM, Frieden C. The Binding of Apolipoprotein E to Oligomers and Fibrils of Amyloid-β Alters the Kinetics of Amyloid Aggregation. Biochemistry. 2014;53(40):6323-6331. https://doi.org/10.1021/bi5008172
39. Chia S, Flagmeier P, Habchi J, et al. Monomeric and fibrillar α-synuclein exert opposite effects on the catalytic cycle that promotes the proliferation of Aβ42 aggregates. Proc Natl Acad Sci U S A. 2017;114(30):8005-8010. https://doi.org/10.1073/pnas.1700239114
40. Zhao Y, Zheng Q, Hong Y, et al. β2-Microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer’s disease model mice. Nat Neurosci. 2023;26(7):1170-1184. https://doi.org/10.1038/s41593-023-01352-1
41. Zhao Y, Zheng Q, Hong Y, et al. β2-Microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer’s disease model mice. Nat Neurosci. 2023;26(7):1170-1184. https://doi.org/10.1038/s41593-023-01352-1
42. Hardy JA, Higgins GA. Alzheimer’s Disease: The Amyloid Cascade Hypothesis. Science. 1992;256(5054):184-185. https://doi.org/10.1126/science.1566067
43. TCW J, Goate AM. Genetics of β-Amyloid Precursor Protein in Alzheimer’s Disease. Cold Spring Harb Perspect Med. 2017;7(6):a024539. https://doi.org/10.1101/cshperspect.a024539
44. Sims JR, Zimmer JA, Evans CD, et al. Donanemab in Early Symptomatic Alzheimer Disease. JAMA. 2023;330(6):512-527. https://doi.org/10.1001/jama.2023.13239
45. De Strooper B, Karran E. The Cellular Phase of Alzheimer’s Disease. Cell. 2016;164(4):603-615. https://doi.org/10.1016/j.cell.2015.12.056
46. Nelson PT, Alafuzoff I, Bigio EH, et al. Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature. J Neuropathol Exp Neurol. 2012;71(5):362-381. https://doi.org/10.1097/NEN.0b013e31825018f7
47. Medina M, Avila J. Editorial: Untangling the Role of Tau in Physiology and Pathology. Front Aging Neurosci. 2020;12:146. https://doi.org/10.3389/fnagi.2020.00146
48. Lei P, Ayton S, Finkelstein DI, et al. Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med. 2012;18(2):291-295. https://doi.org/10.1038/nm.2613
49. Giannakopoulos P, Herrmann FR, Bussière T, et al. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease. Neurology. 2003;60(9):1495-1500. https://doi.org/10.1212/01.wnl.0000063311.58879.01
50. Crary JF, Trojanowski JQ, Schneider JA, et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol (Berl). 2014;128(6):755-766. https://doi.org/10.1007/s00401-014-1349-0
51. Zhang Y, Wu KM, Yang L, Dong Q, Yu JT. Tauopathies: new perspectives and challenges. Mol Neurodegener. 2022;17:28. https://doi.org/10.1186/s13024-022-00533-z
52. Wesseling H, Mair W, Kumar M, et al. Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease. Cell. 2020;183(6):1699-1713.e13. https://doi.org/10.1016/j.cell.2020.10.029
53. Perry G, Friedman R, Shaw G, Chau V. Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci U S A. 1987;84(9):3033-3036. https://doi.org/10.1073/pnas.84.9.3033
54. Luo HB, Xia YY, Shu XJ, et al. SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination. Proc Natl Acad Sci U S A. 2014;111(46):16586-16591. https://doi.org/10.1073/pnas.1417548111
55. Sohn PD, Tracy TE, Son HI, et al. Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment. Mol Neurodegener. 2016;11:47. https://doi.org/10.1186/s13024-016-0109-0
56. Cohen TJ, Guo JL, Hurtado DE, et al. The acetylation of tau inhibits its function and promotes pathological tau aggregation. Nat Commun. 2011;2:252. https://doi.org/10.1038/ncomms1255
57. Funk KE, Thomas SN, Schafer KN, et al. Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity. Biochem J. 2014;462(1):77-88. https://doi.org/10.1042/BJ20140372
58. Liu F, Zaidi T, Iqbal K, Grundke-Iqbal I, Merkle RK, Gong CX. Role of glycosylation in hyperphosphorylation of tau in Alzheimer’s disease. FEBS Lett. 2002;512(1-3):101-106. https://doi.org/10.1016/S0014-5793(02)02228-7
59. Liu F, Shi J, Tanimukai H, et al. Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer’s disease. Brain. 2009;132(7):1820-1832. https://doi.org/10.1093/brain/awp099
60. Zhao X, Kotilinek LA, Smith B, et al. Caspase-2 cleavage of tau reversibly impairs memory. Nat Med. 2016;22(11):1268-1276. https://doi.org/10.1038/nm.4199
61. Gamblin TC, Chen F, Zambrano A, et al. Caspase cleavage of tau: Linking amyloid and neurofibrillary tangles in Alzheimer’s disease. Proc Natl Acad Sci U S A. 2003;100(17):10032-10037. https://doi.org/10.1073/pnas.1630428100
62. Zhang Z, Song M, Liu X, et al. Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer’s disease. Nat Med. 2014;20(11):1254-1262. https://doi.org/10.1038/nm.3700
63. Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol (Berl). 2006;112(4):389-404. https://doi.org/10.1007/s00401-006-0127-z
64. Gibbons GS, Lee VMY, Trojanowski JQ. Mechanisms of Cell-to-Cell Transmission of Pathological Tau. JAMA Neurol. 2019;76(1):101-108. https://doi.org/10.1001/jamaneurol.2018.2505
65. Tan JX, Finkel T. A phosphoinositide signalling pathway mediates rapid lysosomal repair. Nature. 2022;609(7928):815-821. https://doi.org/10.1038/s41586-022-05164-4
66. He Z, Guo JL, McBride JD, et al. Amyloid-β plaques enhance Alzheimer’s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med. 2018;24(1):29-38. https://doi.org/10.1038/nm.4443
67. Goel P, Chakrabarti S, Goel K, Bhutani K, Chopra T, Bali S. Neuronal cell death mechanisms in Alzheimer’s disease: An insight. Front Mol Neurosci. 2022;15:937133. https://doi.org/10.3389/fnmol.2022.937133
68. Balusu S, Horré K, Thrupp N, et al. MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease. Science. 2023;381(6663):1176-1182. https://doi.org/10.1126/science.abp9556
69. Tan MS, Tan L, Jiang T, et al. Amyloid-β induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer’s disease. Cell Death Dis. 2014;5(8):e1382. https://doi.org/10.1038/cddis.2014.348
70. Bao WD, Pang P, Zhou XT, et al. Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease. Cell Death Differ. 2021;28(5):1548-1562. https://doi.org/10.1038/s41418-020-00685-9
71. Suelves N, Saleki S, Ibrahim T, et al. Senescence-related impairment of autophagy induces toxic intraneuronal amyloid-β accumulation in a mouse model of amyloid pathology. Acta Neuropathol Commun. 2023;11:82. https://doi.org/10.1186/s40478-023-01578-x
72. Paudel B, Jeong SY, Martinez CP, et al. Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging. Nat Commun. 2024;15:264. https://doi.org/10.1038/s41467-023-44465-8
73. Araque Caballero MÁ, Suárez-Calvet M, Duering M, et al. White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease. Brain. 2018;141(10):3065-3080. https://doi.org/10.1093/brain/awy229
74. Mathys H, Peng Z, Boix CA, et al. Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer’s disease pathology. Cell. 2023;186(20):4365-4385.e27. https://doi.org/10.1016/j.cell.2023.08.039
75. Kenigsbuch M, Bost P, Halevi S, et al. A shared disease-associated oligodendrocyte signature among multiple CNS pathologies. Nat Neurosci. 2022;25(7):876-886. https://doi.org/10.1038/s41593-022-01104-7
76. Depp C, Sun T, Sasmita AO, et al. Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease. Nature. 2023;618(7964):349-357. https://doi.org/10.1038/s41586-023-06120-6
77. Mahmoudi E, Sadaghiyani S, Lin P, et al. Diagnosis of Alzheimer’s disease and related dementia among people with multiple sclerosis: Large cohort study, USA. Mult Scler Relat Disord. 2022;57:103351. https://doi.org/10.1016/j.msard.2021.103351
78. Jansen IE, Savage JE, Watanabe K, et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat Genet. 2019;51(3):404-413. https://doi.org/10.1038/s41588-018-0311-9
79. Karch CM, Goate AM. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 2015;77(1):43-51. https://doi.org/10.1016/j.biopsych.2014.05.006
80. Dani M, Wood M, Mizoguchi R, et al. Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease. Brain J Neurol. 2018;141(9):2740-2754. https://doi.org/10.1093/brain/awy188
81. Haney MS, Pálovics R, Munson CN, et al. APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia. Nature. 2024;628(8006):154-161. https://doi.org/10.1038/s41586-024-07185-7
82. Streit WJ, Braak H, Xue QS, Bechmann I. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease. Acta Neuropathol (Berl). 2009;118(4):475-485. https://doi.org/10.1007/s00401-009-0556-6
83. Millet A, Ledo JH, Tavazoie S. An Exhausted-Like Microglial Population Accumulates in Aged and APOE4 Genotype Alzheimer’s Brains. Immunity. 2024;57(1):153-170.e6. https://doi.org/10.1016/j.immuni.2023.12.001
84. Xiong X, James BT, Boix CA, et al. Epigenomic dissection of Alzheimer’s disease pinpoints causal variants and reveals epigenome erosion. Cell. 2023;186(20):4422-4437.e21. https://doi.org/10.1016/j.cell.2023.08.040
85. Fu H, Liu B, Frost JL, et al. Complement Component C3 and Complement Receptor Type 3 Contribute to the Phagocytosis and Clearance of Fibrillar Aβ by Microglia. Glia. 2012;60(6):993-1003. https://doi.org/10.1002/glia.22331
86. Doens D, Fernández PL. Microglia receptors and their implications in the response to amyloid β for Alzheimer’s disease pathogenesis. J Neuroinflammation. 2014;11:48. https://doi.org/10.1186/1742-2094-11-48
87. Litvinchuk A, Wan YW, Swartzlander DB, et al. Complement C3aR inactivation attenuates tau pathology and reverses an immune network deregulated in tauopathy models and Alzheimer’s disease. Neuron. 2018;100(6):1337-1353.e5. https://doi.org/10.1016/j.neuron.2018.10.031
88. Asai H, Ikezu S, Tsunoda S, et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci. 2015;18(11):1584-1593. https://doi.org/10.1038/nn.4132
89. Xu Z, Xiao N, Chen Y, et al. Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits. Mol Neurodegener. 2015;10:58. https://doi.org/10.1186/s13024-015-0056-1
90. Kraft AW, Hu X, Yoon H, et al. Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice. FASEB J. 2013;27(1):187-198. https://doi.org/10.1096/fj.12-208660
91. Jiwaji Z, Tiwari SS, Avilés-Reyes RX, et al. Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology. Nat Commun. 2022;13:135. https://doi.org/10.1038/s41467-021-27702-w
92. Mothes T, Portal B, Konstantinidis E, et al. Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology. Acta Neuropathol Commun. 2023;11:97. https://doi.org/10.1186/s40478-023-01589-8
93. Martini-Stoica H, Cole AL, Swartzlander DB, et al. TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading. J Exp Med. 2018;215(9):2355-2377. https://doi.org/10.1084/jem.20172158
94. Wang B, Martini-Stoica H, Qi C, et al. TFEB–vacuolar ATPase signaling regulates lysosomal function and microglial activation in tauopathy. Nat Neurosci. 2023;27(1):48. https://doi.org/10.1038/s41593-023-01494-2
95. Gaikwad S, Puangmalai N, Bittar A, et al. Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer’s disease and frontotemporal dementia. Cell Rep. 2021;36(3):109419. https://doi.org/10.1016/j.celrep.2021.109419
96. Živanović M, Trenkić AA, Milošević V, et al. The role of magnetic resonance imaging in the diagnosis and prognosis of dementia. Biomol Biomed. 2023;23(2):209-224. https://doi.org/10.17305/bjbms.2022.8085
97. Iaccarino L, Sala A, Perani D, Initiative the ADN. Predicting long‐term clinical stability in amyloid‐positive subjects by FDG‐PET. Ann Clin Transl Neurol. 2019;6(6):1113. https://doi.org/10.1002/acn3.782
98. Ossenkoppele R, Schonhaut DR, Schöll M, et al. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease. Brain. 2016;139(5):1551-1567. https://doi.org/10.1093/brain/aww027
99. Lewczuk P, Matzen A, Blennow K, et al. Cerebrospinal Fluid Aβ42/40 Corresponds Better than Aβ42 to Amyloid PET in Alzheimer’s Disease. J Alzheimers Dis. 55(2):813-822. https://doi.org/10.3233/JAD-160722
100. Gonzalez-Ortiz F, Turton M, Kac PR, et al. Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration. Brain. 2022;146(3):1152-1165. https://doi.org/10.1093/brain/awac407
101. Suárez‐Calvet M, Karikari TK, Ashton NJ, et al. Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer’s continuum when only subtle changes in Aβ pathology are detected. EMBO Mol Med. 2020;12(12):e12921. https://doi.org/10.15252/emmm.202012921
102. Barthélemy NR, Salvadó G, Schindler SE, et al. Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests. Nat Med. 2024;30(4):1085-1095. https://doi.org/10.1038/s41591-024-02869-z
103. Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease. JAMA Neurol. 2019;76(7):791-799. https://doi.org/10.1001/jamaneurol.2019.0765
104. Cicognola C, Janelidze S, Hertze J, et al. Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment. Alzheimers Res Ther. 2021;13:68. https://doi.org/10.1186/s13195-021-00804-9
105. Knopman DS, Amieva H, Petersen RC, et al. Alzheimer disease. Nat Rev Dis Primer. 2021;7(1):33. https://doi.org/10.1038/s41572-021-00269-y
106. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in Early Alzheimer’s Disease. N Engl J Med. 2023;388(1):9-21. https://doi.org/10.1056/NEJMoa2212948
107. Congdon EE, Ji C, Tetlow AM, Jiang Y, Sigurdsson EM. Tau-targeting therapies for Alzheimer disease: current status and future directions. Nat Rev Neurol. 2023;19(12):715. https://doi.org/10.1038/s41582-023-00883-2
108. Roberts M, Sevastou I, Imaizumi Y, et al. Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer’s disease. Acta Neuropathol Commun. 2020;8:13. https://doi.org/10.1186/s40478-020-0884-2
109. Mummery CJ, Börjesson-Hanson A, Blackburn DJ, et al. Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial. Nat Med. 2023;29(6):1437-1447. https://doi.org/10.1038/s41591-023-02326-3
110. Wang S, Mustafa M, Yuede CM, et al. Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer’s disease model. J Exp Med. 2020;217(9):e20200785. https://doi.org/10.1084/jem.20200785
111. Dubois B, López‑Arrieta J, Lipschitz S, et al. Correction: Masitinib for mild-to-moderate Alzheimer’s disease: results from a randomized, placebo-controlled, phase 3, clinical trial. Alzheimers Res Ther. 2023;15:85. https://doi.org/10.1186/s13195-023-01230-9
112. Adaikkan C, Middleton SJ, Marco A, et al. Gamma Entrainment Binds Higher Order Brain Regions and Offers Neuroprotection. Neuron. 2019;102(5):929-943.e8. https://doi.org/10.1016/j.neuron.2019.04.011
113. Soula M, Martín-Ávila A, Zhang Y, et al. Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer’s disease model mice. Nat Neurosci. 2023;26(4):570-578. https://doi.org/10.1038/s41593-023-01270-2
114. Da X, Hempel E, Ou Y, et al. Noninvasive Gamma Sensory Stimulation May Reduce White Matter and Myelin Loss in Alzheimer’s Disease. J Alzheimers Dis. 97(1):359-372. https://doi.org/10.3233/JAD-230506
115. Bogucka A, Kotkowiak A, Knychalska K, et al. The Role of Diet, Physical Activity, and Lifestyle in Alzheimer’s Disease Prevention: A Literature Review. Journal of Education, Health and Sport. 2025;80:60011. https://doi.org/10.12775/JEHS.2025.80.60011
116. Paśnik J, Sendecka G, Kistela N, Hądzlik I, Durowicz M, Piotrowski J. Impact of physical activity on the development of Alzheimer’s disease. Journal of Education, Health and Sport. 2024;71:51112. https://doi.org/10.12775/JEHS.2024.71.51112
117. Haber M, Kula P, Juśkiewicz A, et al. Physical Exercise as a Strategy for Prevention and Management of Alzheimer’s Disease Progression. Journal of Education, Health and Sport. 2024;67:55034. https://doi.org/10.12775/JEHS.2024.67.55034
118. Lachowska J, Senior K, Smandek J, Mielczarek M, Sroczyńska P, Sroczyński J. The Effect of Physical Activity on Alzheimer’s Disease - Systematic Review. Quality in Sport. 2025;37:57782. https://doi.org/10.12775/QS.2024.37.57782
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Copyright (c) 2026 Igor Nowiński, Pola Kobryń, Dawid Ocicki, Michał Bojarski, Michał Kwiatkowski, Michał Musielak, Iga Kobryń, Aleksandra Zybert, Aleksandra Borowska, Jakub Grabowski
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