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KMID : 1142620220140020073
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Korea Aging Friendly Industry Association
2022 Volume.14 No. 2 p.73 ~ p.84
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Tau Phosphorylation at Serine 396: Clinical Implications at the Preclinical Stage of Alzheimer’s Disease
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Noh Min-Young
Sung Won-Jae
de Leon Mony
Pirraglia Elizabeth
Kim Hee-Jin
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Abstract
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Objective: Two core pathologies of Alzheimer's disease (AD), abnormal amyloid-beta protein deposition and increased hyper-phosphorylation of tau protein, vary according to the stage of disease. We investigated whether tau hyper-phosphorylation at serine 396 in the extra-neuronal stage of neurofibrillary tangles as an early biomarker.
Methods: We studied 24 individuals with AD, 16 cognitive healthy normal controls (HC), and 19 individuals with mild cognitive impairment (MCI). We analysed cerebrospinal fluid concentrations of β-amyloid 1-40 (Aβ40), β-amyloid 1-42 (Aβ42) using sandwich ELISAs and Innotest for total tau (T-tau), phosphorylated tau 231, and phosphorylated tau 396 (P-tau 231, P-tau 396). Cerebrospinal fluid biomarkers of AD were evaluated for an association with clinical parameters and other related biological data.
Results: Levels of P-tau 396 were lowest in HC compared to those in the AD and MCI groups (each p<0.001, and p=0.009). When Z-scores of total tau, P-tau 231, and P-tau 396 were compared among groups, the AD patients showed higher Z-scores of total tau and P-tau 231 than the other two groups. Differences in Z-score of P-tau 396 were observed between HC and the AD (p < 0.001) and MCI groups. The levels of Aβ42, Aβ40, T- tau, and P-tau 231 were correlated with clinical data and medial temporal atrophy in the AD and MCI groups.
Conclusion: The levels of P-tau 396 in the cerebrospinal fluid showed significant differences between HC and the other two groups. Levels of P-tau 396 could be useful as a biomarker to predict disrupted neuronal integrity before the disease.
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KEYWORD
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Alzheimer’s disease, Biomarker, Cerebrospinal fluid, Tau
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