Author(s):
Abdalkareem Maghmomeh, Lubana Alkhoder, Batoul Turk, Aya Habbal, Daed AL-Afandi
Email(s):
abdalkareem.maghmomeh@wpu.edu.sy , lubana.alkhoder@wpu.edu.sy , batoulturk2001@gmail.com , ahabbal070@gmail.com , daadooaf@gmail.com
DOI:
10.52711/0974-360X.2026.00688
Address:
Abdalkareem Maghmomeh1, Lubana Alkhoder2, Batoul Turk3, Aya Habbal3, Daed AL-Afandi3
1Department of Biochemistry, Faculty of Pharmacy, AL-Watanyia Private University, Hama, Syria.
2Department of Laboratory Diagnosis, Faculty of Pharmacy, AL-Watanyia Private University, Hama, Syria.
3Faculty of Pharmacy, AL-Watanyia Private University, Hama, Syria.
*Corresponding Author
Published In:
Volume - 19,
Issue - 10,
Year - 2026
ABSTRACT:
Alzheimer's. disease is a degenerative brain illness that impairs. memory and cognitive function. It is the leading cause of dementia and the seventh greatest cause of mortality worldwide. The condition starts with minor. memory loss and progresses to a loss of capacity. to speak and engage with the surroundings. Alzheimer's. disease has three stages: preclinical. illness, mild. cognitive and/or behavioral. impairment, and dementia. Poor diagnosis is a substantial impediment to illness management, delaying progression, and easing symptoms. In this study, we look into diagnostic biomarkers that can predict the emergence of Alzheimer's disease in the preclinical phases. which allow for the slowing of disease. progression and the introduction of new avenues in the hunt for a cure to treat the disease before it develops.
Cite this article:
Abdalkareem Maghmomeh, Lubana Alkhoder, Batoul Turk, Aya Habbal, Daed AL-Afandi. Early Prognosis of Alzheimer's Disease: Diagnostic Biomarker Review Article. Research Journal Pharmacy and Technology. 2026;19(10):4938-6. doi: 10.52711/0974-360X.2026.00688
Cite(Electronic):
Abdalkareem Maghmomeh, Lubana Alkhoder, Batoul Turk, Aya Habbal, Daed AL-Afandi. Early Prognosis of Alzheimer's Disease: Diagnostic Biomarker Review Article. Research Journal Pharmacy and Technology. 2026;19(10):4938-6. doi: 10.52711/0974-360X.2026.00688 Available on: https://rjptonline.org/AbstractView.aspx?PID=2026-19-10-64
REFERENCES:
1. World Health Organization. Global status report on the public health response to dementia. Geneva: World Health Organization; 2023.
2. Guerreiro R, Bras J. The age factor in Alzheimer's disease. Genome Med. 2015; 7(1). https://doi.org/10.1186/s13073-015-0232-5
3. Ma Y, Brettschneider J, Collingwood JF. A systematic review and meta-analysis of cerebrospinal fluid amyloid and tau levels identifies mild cognitive impairment patients progressing to Alzheimer's disease. Biomedicines. 2022; 10(7): 1713.
4. National Institute on Aging. Alzheimer’s Disease Fact Sheet. Bethesda (MD): NIA; [n.d.].
5. Shalini VP, Kalaiselvi. A study to assess the knowledge, and attitude regarding Alzheimer’s dementia among adults in Nanchiyampalayam at Dharapuram with a view of conducting an awareness programme on prevention of Alzheimer’s Dementia. Int J Adv Nurs Manag. 2020; 8(2): 149–53. doi:10.5958/2454-2652.2020.00035.9
6. Van Cauwenberghe C, Van Broeckhoven C, Sleegers K. The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med. 2016; 18(5): 421–30.
7. Porsteinsson AP, Isaacson RE, Knox S, Sabbagh MN, Rubino I. Diagnosis of early Alzheimer’s disease: clinical practice in 2021. J Prev Alzheimers Dis. 2021; 1–16.
8. Shalini VP, Kalaiselvi. A study to assess the knowledge, and attitude regarding Alzheimer’s dementia among adults in Nanchiyampalayam at Dharapuram with a view of conducting an awareness programme on prevention of Alzheimer’s Dementia. Int J Adv Nurs Manag. 2020; 8(2): 149–53. doi:10.5958/2454-2652.2020.00035.9
9. Ridha BH, Barnes J, Bartlett JW, Godbolt AK, Pepple T, Rossor MN, Fox NC. Tracking atrophy progression in familial Alzheimer's disease: a serial MRI study. Lancet Neurol. 2006; 5(10): 828–34.
10. Mendez MF. Early-onset Alzheimer disease and its variants. Continuum (Minneap Minn). 2019; 25(1): 34–51.
11. Braskie MN, Jahanshad N, Stein DJ, Barysheva M, McMahon KL, De Zubicaray GI, et al. Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults. J Neurosci. 2011; 31(18): 6764–70.
12. Adav SS, Sze SK. Insight of brain degenerative protein modifications in the pathology of neurodegeneration and dementia by proteomic profiling. Mol Brain. 2016; 9(1).
13. Tran L, Ha-Duong T. Exploring the Alzheimer amyloid-β peptide conformational ensemble: a review of molecular dynamics approaches. Peptides. 2015; 69: 86–91.
14. Horwich AL. Protein aggregation in disease: a role for folding intermediates forming specific multimeric interactions. J Clin Invest. 2002;.
15. Rajesh Kumar D, Siva Shankar M, Prathap Reddy P, Ram Sarath Kumar B, Sumalatha N. A review on Alzheimer’s disease. Res J Pharmacology Pharmacodynamics. 2014; 6(1): 59–63.
16. Selkoe DJ. Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases. Nat Cell Biol. 2004; 6(11): 1054–61.
17. Blessed G, Tomlinson B, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968; 114(512): 797–811.
18. Bertram L, Tanzi RE. The genetics of Alzheimer's disease. In: Progress in Molecular Biology and Translational Science. Academic Press; 2012. p. 79–100.
19. Choudhury S, Vellapandian C. Alzheimer’s disease pathophysiology and its implications. Res J Pharm Technol. 2019; 12(4): 2045–8. doi:10.5958/0974-360X.2019.00338.X
20. Pal T, Das M. Review of Alzheimer’s disease’s animal model with its pathophysiology and drug discovery. Asian J Res Pharm Sci. 2024; 14(1): 34–2. doi:10.52711/2231-5659.2024.00006
21. Armstrong RA. What causes Alzheimer's disease? Folia Neuropathol. 2013;51(3):169–88.
22. Bloom GS. Amyloid-β and Tau. JAMA Neurol. 2014; 71(4): 505.
23. Zheng H, Koo EH. The amyloid precursor protein: beyond amyloid. Mol Neurodegener. 2006; 1(1).
24. Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 1999; 286(5440): 735–41.
25. Tackenberg C, Nitsch RM. The secreted APP ectodomain sAPPα, but not sAPPβ, protects neurons against Aβ oligomer-induced dendritic spine loss and increased tau phosphorylation. Mol Brain. 2019; 12(1).
26. Pol RP, Naikwade NS, Dias RJ. Targeting Aβ protein in Alzheimer’s disease. Res J Pharm Technol. 2020; 13(2): 1004–8. doi:10.5958/0974-360X.2020.00186.9
27. Chen ZR, Huang JB, Yang SL, Hong FF. Role of cholinergic signaling in Alzheimer's disease. Molecules. 2022; 27(6): 1816.
28. Avila J, Lucas JJ, Perez M, Hernandez F. Role of tau protein in both physiological and pathological conditions. Physiol Rev. 2004; 84(2): 361–84.
29. Mitchison T, Kirschner M. Cytoskeletal dynamics and nerve growth. Neuron. 1988; 1(9): 761–72.
30. Gonzalez-Billault C, Engelke M, Jimenez-Mateos EM, Wandosell F, Caceres A, Avila J. Participation of structural microtubule-associated proteins in the development of neuronal polarity. J Neurosci Res. 2002; 67(6): 713–9.
31. Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proc Natl Acad Sci U S A. 1975; 72(5): 1858–62.
32. Kimura T, Whitcomb DJ, Jo J, Regan P, Piers T, Heo S, et al. Microtubule-associated protein tau is essential for long-term depression in the hippocampus. Philos Trans R Soc Lond B Biol Sci. 2018; 369(1633).
33. Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. 1989; 3(4): 519–26.
34. Baudier J, Cole RD. Phosphorylation of tau proteins to a state like that in Alzheimer's brain is catalyzed by a calcium/calmodulin-dependent kinase and modulated by phospholipids. J Biol Chem. 1987; 262(36): 17577–83.
35. Togo T, Akiyama H, Iseki E, Kondo H, Ikeda K, Kato M, et al. Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases. J Neuroimmunol. 2002; 124(1–2): 83–92.
36. Ballatore C, Lee VM, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci. 2007; 8(9): 663–72.
37. Guo T, Lee VM. Neurofibrillary tangle-like tau pathology induced by synthetic tau fibrils in primary neurons over-expressing mutant tau. FEBS Lett. 2011; 585(5): 703–10.
38. Iqbal K, Alonso AD, Chen S, Chohan MO, El-Akkad E, Gong CX, et al. Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta. 2000; 1502(1): 110–21.
39. Vijey Aanandhi M, Niventhi A, Rujaswini T, Hemalatha CN, Praveen D. A comprehensive review on the role of tau proteins in Alzheimer’s pathology. Res J Pharm Technol. 2018; 11(2): 788–90. doi:10.5958/0974-360X.2018.00149.X
40. Rukmangadachar LA. Amyloid Beta Peptide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
41. Vijey Aanandhi M, Yeshwanth Prasanna Kumar B, Ranadheer Chowdary P, Praveen D. A review on the role of presenilin in Alzheimer’s disease. Res J Pharm Technol. 2018; 11(5): 2149–51. doi:10.5958/0974-360X.2018.00397.9
42. Holtzman DM, Morris JC, Goate A. Alzheimer's disease: the challenge of the second century. Sci Transl Med. 2011; 3(77).
43. Thinakaran G, Koo EH. Amyloid precursor protein trafficking, processing, and function. J Biol Chem. 2008; 283(44): 29615–9.
44. Prince M, Bryce R, Ferri C. World Alzheimer report 2011: the benefits of early diagnosis and intervention. London: Alzheimer’s Disease International; 2011.
45. 2021 Alzheimer’s disease facts and figures. Alzheimers Dement. 2021; 17(3): 327–406.
46. Dubois B, Feldman H, Jacova C, Cummings JL, DeKosky ST, Barberger-Gateau P, et al. Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol. 2010; 9(11): 1118–27.
47. Vermunt L, Sikkes SA, Hout A, Handels R, Bos I, van der Flier WM, et al. Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype. Alzheimers Dement. 2019; 15(7): 888–98.
48. Dubois B, Hampel H, Feldman HH, Scheltens P, Aisen P, Andrieu S, et al. Preclinical Alzheimer's disease: definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016; 12(3): 292–323. https://doi.org/10.1016/j.jalz.2016.02.002
49. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the NIA-AA workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3): 280–92.
50. Knopman DS, Jack CR, Wiste HJ, Weigand SD, Vemuri P, Lowe VJ, et al. Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology. 2012; 78(20): 1576–82.
51. Knopman DS, Parisi J, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, et al. Neuropathology of cognitively normal elderly. J Neuropathol Exp Neurol. 2003; 62(11): 1087–95.
52. Cho SH, Woo S, Kim C, Kim HJ, Jang H, Kim BC, et al. Disease progression modelling from preclinical Alzheimer's disease to AD dementia. Sci Rep. 2021; 11(1).
53. Kazim SF, Iqbal K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease. Mol Neurodegener. 2016; 11(1).
54. Tolbert S, Liu YW, Hellegers C, Petrella JR, Weiner MW, Wong TY, Doraiswamy PM. Financial management skills in aging, MCI and dementia: cross sectional relationship to 18F-florbetapir PET cortical β-amyloid deposition. J Prev Alzheimers Dis. 2019; 1–9.
55. Anderson ND. State of the science on mild cognitive impairment (MCI). CNS Spectr. 2019;24(1):78–87.
56. Manafikhi R, Haik MB, Lahdo R, AlQuoubaili F. Plasma amyloid β levels in Alzheimer's disease and cognitively normal controls in Syrian population. Med J Islam Repub Iran. 2021; 35: 19.
57. Toledo JB, Shaw LM, Trojanowski JQ. Plasma amyloid beta measurements—a desired but elusive Alzheimer’s disease biomarker. Alzheimers Res Ther. 2013; 5(2): 8.
58. Wilson MR, Yerbury JJ, Poon S. Potential roles of abundant extracellular chaperones in the control of amyloid formation and toxicity. Mol Biosyst. 2008; 4(1): 42–52.
59. Bloudek LM, Spackman DE, Blankenburg M, Sullivan SD. Review and meta-analysis of biomarkers and diagnostic imaging in Alzheimer's disease. J Alzheimers Dis. 2011;26(4):627–45.
60. Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006; 5(3): 228–34.
61. Scheltens P, Blennow K, Breteler MM, De Strooper B, Frisoni GB, Salloway S, van der Flier WM. Alzheimer's disease. Lancet. 2016; 388(10043): 505–17.
62. Jack CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013; 12(2): 207–16.
63. Babić MM, Štrac DŠ, Muck-Seler D, Pivac N, Stanić G, Hof PR, Šimić G. Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease. CroatMedJ.2014;55(4):347–65.
64. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004; 256(3): 183–94.
65. Chong MS, Sahadevan S. Preclinical Alzheimer's disease: diagnosis and prediction of progression. Lancet Neurol. 2005; 4(9): 576–9.
66. Visser PJ, Verhey FR, Hofman P, Scheltens P, Jolles J. Medial temporal lobe atrophy predicts Alzheimer's disease in patients with minor cognitive impairment. J Neurol Neurosurg Psychiatry. 2002; 72(4): 491–7.
67. Dickerson BC, Goncharova II, Sullivan MK, Forchetti C, Wilson RJ, Bennett DP, et al. MRI-derived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer's disease. Neurobiol Aging. 2001; 22(5): 747–54.
68. Jack CR, Shiung MM, Gunter JL, O'Brien PT, Weigand SD, Knopman DS, et al. Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology. 2004; 62(4): 591–600.
69. Jack CR, Bennett DA, Blennow K, Carrillo MC, Feldman H, Frisoni GB, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016; 87(5): 539–47.
70. Malarkodi Velraj N, Lavaniya. Alzheimer disease and a potential role of herbs—a review. Res J Pharm Technol. 2018; 11(6): 2695–700. doi:10.5958/0974-360X.2018.00498.5
71. Patel JB, Patel KM, Shah DH, Patel JS, Garg CS, Brahmbhatt KJ, Sen DJ. Functional magnetic resonance imaging: a new diversion in medical diagnosis. Res J Pharm Technol. 2011; 4(8): 1167–76.
72. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Ann Neurol. 2004; 55(3): 306–19.
73. Buerger K, Ewers M, Pirttilä T, Zinkowski R, Alafuzoff I, Teipel SJ, et al. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease. Brain. 2006; 129(11): 3035–41.
74. Arai H, Terajima M, Miura M, Higuchi S, Muramatsu T, Machida N, et al. Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer's disease. Ann Neurol. 1995; 38(4): 649–52.
75. Petrie EC, Cross D, Galasko D, Schellenberg GD, Raskind MA, Peskind ER, Minoshima S. Preclinical evidence of Alzheimer changes. Arch Neurol. 2009; 66(5): 632–7.
76. Bobinski M, De Leon MJ, Wegiel J, DeSanti S, Convit A, Louis LA, et al. The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease. Neuroscience. 1999; 95(3): 721–5.
77. Jack CR, Petersen RC, O'Brien PC, Tangalos EG. MR-based hippocampal volumetry in the diagnosis of Alzheimer's disease. Neurology. 1992; 42(1): 183–8.
78. Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol. 1997; 42(1): 85–94.
79. Moghekar A, Li S, Lu Y, Li M, Wang ML, Albert MS, O'Brien RL. CSF biomarker changes precede symptom onset of mild cognitive impairment. Neurology. 2013; 81(20): 1753–8.
80. Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA. 2009; 302(4): 385–93.
81. Seab JP, Jagust WJ, Wong ST, Roos MS, Reed BR, Budinger TF. Quantitative NMR measurements of hippocampal atrophy in Alzheimer's disease. Magn Reson Med. 1988; 8(2): 200–8.
82. Lewczuk P, Lelental N, Spitzer P, Maler JM, Kornhuber J. Amyloid-β 42/40 cerebrospinal fluid concentration ratio in the diagnostics of Alzheimer's disease: validation of two novel assays. J Alzheimers Dis. 2014; 43(1): 183–91.
83. Hesse C, Rosengren L, Andreasen N, Davidsson P, Vanderstichele H, Vanmechelen E, Blennow K. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci Lett. 2001; 297(3): 187–90.
84. Götz J, Chen F, Van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in P301L tau transgenic mice induced by Aβ42 fibrils. Science. 2001; 293(5534): 1491–5.
85. Blennow K, Zetterberg H. Biomarkers for Alzheimer's disease: current status and prospects for the future. J Intern Med. 2018; 284(6): 643–63.
86. Ewers M, Zhong Z, Bürger K, Wallin A, Blennow K, Teipel SJ, et al. Increased CSF-BACE1 activity is associated with ApoE-ε4 genotype in subjects with mild cognitive impairment and Alzheimer's disease. Brain. 2008; 131(5): 1252–8.
87. Blennow K, Hampel H, Weiner MW, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010; 6(3): 131–44.
88. Sämgård K, Zetterberg H, Blennow K, Hansson O, Minthon L, Londos E. Cerebrospinal fluid total tau as a marker of Alzheimer's disease intensity. Int J Geriatr Psychiatry. 2010; 25(4): 403–10.
89. Roe CM, Fagan AM, Grant E, Hassenstab J, Moulder KL, Dreyfus DM, et al. Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later. Neurology. 2013; 80(19): 1784–91.
90. Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/β-amyloid42 ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007; 64(3): 343–9.
91. Morris JC, Roe CM, Xiong C, Fagan AM, Goate A, Holtzman DM, Mintun MA. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol. 2010; 67(1): 122–31.
92. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012; 367(9): 795–804.
93. Cairns NJ, Ikonomovic MD, Benzinger TL, Storandt M, Fagan AM, Shah AR, et al. Absence of Pittsburgh compound B detection of cerebral amyloid β in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease. Arch Neurol. 2009; 66(12): 1557–62.
94. Fagan AM, Head D, Shah AR, Marcus DS, Mintun MA, Morris JC, Holtzman DM. Decreased cerebrospinal fluid Aβ42 correlates with brain atrophy in cognitively normal elderly. Ann Neurol. 2009; 65(2): 176–83.