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. 2022 Sep 16;23(18):10831.
doi: 10.3390/ijms231810831.

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer's Disease from Other Neurological Disorders

Tommaso Piccoli  1 , Valeria Blandino  1 , Laura Maniscalco  2 , Domenica Matranga  2 , Fabiola Graziano  1 , Fabrizio Guajana  1 , Luisa Agnello  3 , Bruna Lo Sasso  3   4 , Caterina Maria Gambino  3   4 , Rosaria Vincenza Giglio  3   4 , Vincenzo La Bella  5 , Marcello Ciaccio  3 , Tiziana Colletti  5
Affiliations

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer's Disease from Other Neurological Disorders

Tommaso Piccoli et al. Int J Mol Sci. .

Abstract

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn alone. Regression analyses showed an association of higher Ng concentrations with MMSE < 24, pathological Aβ 42/40 ratios, pTau, tTau and the ApoEε4 genotype. Aβ 42/Ng was associated with MMSE < 24, an AD-related FDG-PET pattern, the ApoEε4 genotype, pathological Aβ 42 levels and Aβ 42/40 ratios, pTau, and tTau. Moreover, APO-Eε4 carriers showed higher Ng concentrations than non-carriers. Our results support the idea that the Aβ 42/Ng ratio is a reliable index of synaptic dysfunction/degeneration able to discriminate AD from other neurological conditions.

Keywords: Alzheimer’s disease; biomarkers; neurogranin; α-synuclein.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CSF Ng (a) and α-Syn (b) levels in AD and n-ND patients. Data are expressed as medians with interquartile ranges (IQRs). We used the Kruskal–Wallis test with Dunn’s post hoc test. p < 0.05 was considered statistically significant and is indicated with bold font. (c) Receiver operating characteristic (ROC) analyses and (d) area under curve (AUC) of CSF Ng and α-Syn in AD vs. n-ND.
Figure 2
Figure 2
CSF Ng (a) and α-Syn (b) levels in AD and n-AD patients. Data are expressed as medians with interquartile ranges (IQRs). We used the Kruskal–Wallis test with Dunn’s post hoc test. p < 0.05 was considered statistically significant and is indicated with bold font. (c) Receiver operating characteristic (ROC) analyses and (d) area under curve (AUC) of CSF Ng and α-Syn in AD vs. n-AD.
Figure 3
Figure 3
CSF neurogranin (a) and α-synuclein (b) levels in AD patients subgrouped based on ApoE ε4 genotypes: ApoE4(+) and ApoE4(−). Data are expressed as medians with interquartile ranges (IQRs) and were analyzed by the Mann–Whitney U test, also indicating the size effect (η2). p-values were corrected for multiplicity by the Holm–Sidak method and are indicated with bold font.
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References

    1. Tzioras M., Davies C., Newman A., Jackson R., Spires-Jones T. Invited Review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 2019;45:327–346. doi: 10.1111/nan.12529. - DOI - PMC - PubMed
    1. Deture M.A., Dickson D.W. The neuropathological diagnosis of Alzheimer’s disease. Mol. Neurodegener. 2019;14:32. doi: 10.1186/s13024-019-0333-5. - DOI - PMC - PubMed
    1. Jack C.R., Knopman D.S., Jagust W.J., Shaw L.M., Aisen P.S., Weiner M.W., Petersen R.C., Trojanowski J.Q. Hypothetical Pathological Cascade in Alheimer’s Disease. Lancet Neurol. 2010;9:1–20. doi: 10.1016/S1474-4422(09)70299-6. - DOI - PMC - PubMed
    1. Agnello L., Piccoli T., Vidali M., Cuffaro L., Lo Sasso B., Iacolino G., Giglio V.R., Lupo F., Alongi P., Bivona G., et al. Diagnostic accuracy of cerebrospinal fluid biomarkers measured by chemiluminescent enzyme immunoassay for Alzheimer disease diagnosis. Scand. J. Clin. Lab. Investig. 2020;80:313–317. doi: 10.1080/00365513.2020.1740939. - DOI - PubMed
    1. Virgilio E., De Marchi F., Contaldi E., Dianzani U., Cantello R., Mazzini L., Comi C. The Role of Tau beyond Alzheimer’s Disease: A Narrative Review. Biomedicines. 2022;10:760. doi: 10.3390/biomedicines10040760. - DOI - PMC - PubMed