Clinical Utility of Cerebrospinal Fluid Aβ42 and Tau Measures in Diagnosing Mild Cognitive Impairment in Early Onset Dementia

Hosseini, Akram A.; Brown, Thomas; Mannino, Luca; Gran, Bruno; Junaid, Kehinde; Mukaetova-Ladinska, Elizabeta B.

Abstract

Background: The differentiation of a preclinical or prodromal Alzheimer's disease (AD) is challenging particularly in patients with early onset Alzheimer's or related dementias (EOARD). We report our experience on diagnostic lumbar puncture to diagnose EOARD at a tertiary neurocognitive referral center in Nottingham, England from March 2018 to October 2020. Objective: To assess amyloid-β42 (Aβ42), total tau, and Thr181-phosphorylated tau (p-tau) measurements in the cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and in relation to their follow-up cognitive performance. Methods: Thirty participants aged 32-68 years old (mean 59 years; 57% female) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, neuroradiological features (MRI, FDG-PET CT) and CSF Aβ42, total tau, and p-tau measurements. Results: Patients with MCI who progressed to AD (prodromal AD) had significantly higher CSF total (797.63 pg/ml) and p-tau (82.31 pg/ml), and lower Aβ42 levels (398.94 pg/ml) in comparison to their counterparts with stable MCI (total tau 303.67 pg/ml, p-tau 43.56 pg/ml, Aβ42 873.44 pg/ml) (p < 0.01 for CSF total and p-tau measures and p < 0.0001 for CSF Aβ42 measures). None of the CSF biomarkers correlated with any of the cognitive performance measures. Principal component analysis confirmed that the clinical diagnosis of MCI secondary to AD, namely prodromal AD (as per NIA-AA criteria) in younger adults, was associated with decreased CSF Aβ42. Conclusion: In early onset AD, low levels of CSF Aβ42 appear to be more sensitive than total and p-tau measures in differentiating AD MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness of making an earlier diagnosis.

Citation

Hosseini, A. A., Brown, T., Mannino, L., Gran, B., Junaid, K., & Mukaetova-Ladinska, E. B. (2022). Clinical Utility of Cerebrospinal Fluid Aβ42 and Tau Measures in Diagnosing Mild Cognitive Impairment in Early Onset Dementia. Journal of Alzheimer's Disease, 87(2), 771-780. https://doi.org/10.3233/JAD-215650

• Journal Article Type: Article
• Acceptance Date: Mar 7, 2022
• Online Publication Date: May 17, 2022
• Publication Date: May 17, 2022
• Deposit Date: Jun 15, 2024
• Publicly Available Date: Jul 4, 2024
• Journal: Journal of Alzheimer's Disease
• Print ISSN: 1387-2877
• Electronic ISSN: 1875-8908
• Publisher: IOS Press
• Peer Reviewed: Peer Reviewed
• Volume: 87
• Issue: 2
• Pages: 771-780
• DOI: https://doi.org/10.3233/JAD-215650
• Public URL: https://nottingham-repository.worktribe.com/output/8309794
• Publisher URL: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215650