Towards Early Diagnosis of Alzheimer's Disease: Advances in Immune-related Blood Biomarkers and Computational Approaches

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 May 9

PMID 38720902

Authors

Sophia Krix

Ella Wilczynski

Neus Falgas

Raquel Sanchez-Valle

Eti Yoles

Uri Nevo

Kuti Baruch

Holger Frohlich

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease has an increasing prevalence in the population world-wide, yet current diagnostic methods based on recommended biomarkers are only available in specialized clinics. Due to these circumstances, Alzheimer's disease is usually diagnosed late, which contrasts with the currently available treatment options that are only effective for patients at an early stage. Blood-based biomarkers could fill in the gap of easily accessible and low-cost methods for early diagnosis of the disease. In particular, immune-based blood-biomarkers might be a promising option, given the recently discovered cross-talk of immune cells of the central nervous system with those in the peripheral immune system. Here, we give a background on recent advances in research on brain-immune system cross-talk in Alzheimer's disease and review machine learning approaches, which can combine multiple biomarkers with further information (e.g. age, sex, APOE genotype) into predictive models supporting an earlier diagnosis. In addition, mechanistic modeling approaches, such as agent-based modeling open the possibility to model and analyze cell dynamics over time. This review aims to provide an overview of the current state of immune-system related blood-based biomarkers and their potential for the early diagnosis of Alzheimer's disease.

References

Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N . Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci. 2006; 9(2):268-75. DOI: 10.1038/nn1629. View

Meier-Stephenson F, Meier-Stephenson V, Carter M, Meek A, Wang Y, Pan L . Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites. Alzheimers Dement (N Y). 2022; 8(1):e12283. PMC: 8985489. DOI: 10.1002/trc2.12283. View

Louveau A, Herz J, Alme M, Salvador A, Dong M, Viar K . CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018; 21(10):1380-1391. PMC: 6214619. DOI: 10.1038/s41593-018-0227-9. View

Baruch K, Deczkowska A, David E, Castellano J, Miller O, Kertser A . Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science. 2014; 346(6205):89-93. PMC: 4869326. DOI: 10.1126/science.1252945. View

Naert G, Rivest S . A deficiency in CCR2+ monocytes: the hidden side of Alzheimer's disease. J Mol Cell Biol. 2013; 5(5):284-93. DOI: 10.1093/jmcb/mjt028. View

Liu D, Cao B, Zhao Y, Huang H, McIntyre R, Rosenblat J . Soluble TREM2 changes during the clinical course of Alzheimer's disease: A meta-analysis. Neurosci Lett. 2018; 686:10-16. DOI: 10.1016/j.neulet.2018.08.038. View

Jack Jr C, Bennett D, Blennow K, Carrillo M, Dunn B, Budd Haeberlein S . NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14(4):535-562. PMC: 5958625. DOI: 10.1016/j.jalz.2018.02.018. View

Miskov-Zivanov N, Turner M, Kane L, Morel P, Faeder J . The duration of T cell stimulation is a critical determinant of cell fate and plasticity. Sci Signal. 2013; 6(300):ra97. PMC: 4074924. DOI: 10.1126/scisignal.2004217. View

Cicognola C, Janelidze S, Hertze J, Zetterberg H, Blennow K, Mattsson-Carlgren N . 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(1):68. PMC: 8005231. DOI: 10.1186/s13195-021-00804-9. View

10.

Chen X, Firulyova M, Manis M, Herz J, Smirnov I, Aladyeva E . Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy. Nature. 2023; 615(7953):668-677. PMC: 10258627. DOI: 10.1038/s41586-023-05788-0. View

11.

Kipnis J, Cohen H, Cardon M, Ziv Y, Schwartz M . T cell deficiency leads to cognitive dysfunction: implications for therapeutic vaccination for schizophrenia and other psychiatric conditions. Proc Natl Acad Sci U S A. 2004; 101(21):8180-5. PMC: 419577. DOI: 10.1073/pnas.0402268101. View

12.

Fukuyama R, Izumoto T, Fushiki S . The cerebrospinal fluid level of glial fibrillary acidic protein is increased in cerebrospinal fluid from Alzheimer's disease patients and correlates with severity of dementia. Eur Neurol. 2001; 46(1):35-8. DOI: 10.1159/000050753. View

13.

Baruch K, Ron-Harel N, Gal H, Deczkowska A, Shifrut E, Ndifon W . CNS-specific immunity at the choroid plexus shifts toward destructive Th2 inflammation in brain aging. Proc Natl Acad Sci U S A. 2013; 110(6):2264-9. PMC: 3568380. DOI: 10.1073/pnas.1211270110. View

14.

Kyrtsos C, Baras J . Studying the role of ApoE in Alzheimer's disease pathogenesis using a systems biology model. J Bioinform Comput Biol. 2013; 11(5):1342003. DOI: 10.1142/S0219720013420031. View

15.

Walker D, Southgate J . The virtual cell--a candidate co-ordinator for 'middle-out' modelling of biological systems. Brief Bioinform. 2009; 10(4):450-61. DOI: 10.1093/bib/bbp010. View

16.

Kim Y, Lee H . PINNet: a deep neural network with pathway prior knowledge for Alzheimer's disease. Front Aging Neurosci. 2023; 15:1126156. PMC: 10380929. DOI: 10.3389/fnagi.2023.1126156. View

17.

Singh D . Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer's disease. J Neuroinflammation. 2022; 19(1):206. PMC: 9382837. DOI: 10.1186/s12974-022-02565-0. View

18.

Kivisakk P, Carlyle B, Sweeney T, Trombetta B, LaCasse K, El-Mufti L . Plasma biomarkers for diagnosis of Alzheimer's disease and prediction of cognitive decline in individuals with mild cognitive impairment. Front Neurol. 2023; 14:1069411. PMC: 10018178. DOI: 10.3389/fneur.2023.1069411. View

19.

Correa S, Eales K . The Role of p38 MAPK and Its Substrates in Neuronal Plasticity and Neurodegenerative Disease. J Signal Transduct. 2012; 2012:649079. PMC: 3389708. DOI: 10.1155/2012/649079. View

20.

Adra S, Sun T, MacNeil S, Holcombe M, Smallwood R . Development of a three dimensional multiscale computational model of the human epidermis. PLoS One. 2010; 5(1):e8511. PMC: 2799518. DOI: 10.1371/journal.pone.0008511. View