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. 2022 Apr 27;14(1):e12314.
doi: 10.1002/dad2.12314. eCollection 2022.

Clinical application of CSF biomarkers for Alzheimer's disease: From rationale to ratios

Femke H Bouwman  1 , Giovanni B Frisoni  2 , Sterling C Johnson  3 , Xiaochun Chen  4 , Sebastiaan Engelborghs  5 , Takeshi Ikeuchi  6 , Claire Paquet  7 , Craig Ritchie  8 , Sasha Bozeat  9 , Frances-Catherine Quevenco  9 , Charlotte Teunissen  10
Affiliations

Clinical application of CSF biomarkers for Alzheimer's disease: From rationale to ratios

Femke H Bouwman et al. Alzheimers Dement (Amst). .

Abstract

Biomarker testing is recommended for the accurate and timely diagnosis of Alzheimer's disease (AD). Using illustrative case narratives we consider how cerebrospinal fluid (CSF) biomarker tests may be used in different presentations of cognitive impairment to facilitate timely and differential diagnosis, improving diagnostic accuracy, providing prognostic information, and guiding personalized management in diverse scenarios. Evidence shows that (1) CSF ratios are superior to amyloid beta (Aβ)1-42 alone; (2) concordance of CSF ratios to amyloid positron emission tomography (PET) is better than Aβ1-42 alone; and (3) phosphorylated tau (p-tau)/Aβ1-42 ratio is superior to p-tau alone. CSF biomarkers are recommended for the exclusion of AD as the underlying cause of cognitive impairment, diagnosis of AD at an early stage, differential diagnosis of AD in individuals presenting with other neuropsychiatric symptoms, accurate diagnosis of AD in an atypical presentation, and for clinical trial enrichment.

Highlights: Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker testing may be underused outside specialist centers.CSF biomarkers improve diagnostic accuracy, guiding personalized management of AD.CSF ratios (amyloid beta [Aβ]1-42/Aβ1-40 and phosphorylated tau/Aβ1-42) perform better than single markers.CSF ratios produce fewer false-negative and false-positive results than individual markers.CSF biomarkers should be included in diagnostic work-up of AD and mild cognitive impairment due to AD.

Keywords: Alzheimer's disease; cerebrospinal fluid biomarkers; diagnosis; mild cognitive impairment.

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Conflict of interest statement

Femke Bouwman received a grant from Optina Dx (Canada), honoraria from Roche, and provided expert testimony for Biogen; all payments were made to the institution. Giovanni B. Frisoni has no competing interests to declare. Sterling C. Johnson received a research grant from Cerveau Technologies paid to the institution, participated in advisory boards for Roche Diagnostics and Prothena, and received an equipment grant from Roche Diagnostics paid to the institution. Xiaochun Chen has no competing interests to declare. Sebastiaan Engelborghs received grants from Janssen Pharmaceutica and ADx Neurosciences paid to the institution; consulting fees from icometrix (paid to institution), Biogen, Roche, and Novartis; and honoraria from Eisai/Pfizer. Takeshi Ikeuchi received grants AMED JP21dk0207049, AMED JP21dk0207045, and AMED JP21ek0109545 paid to the institution, and honoraria from Eisai, Daiichi‐Sankyo, Fuji Film RI Pharma, Ajinomoto, Novartis, and Chugai Pharmaceutical. Claire Paquet is on advisory boards for Roche, Lilly, and Biogen laboratories. Craig Ritchie received consulting fees from Roche, Biogen, Eisai, Sygnature, Actinogen, Eli Lilly, MSD, Signant Health, and Alchemab, and honoraria from Biogen, Roche, and Eisai. Charlotte Teunissen has collaboration contracts with ADx Neurosciences and Quanterix, and grants from Axon NeuroSciences, Biogen, Boehringer, Brainstorm Therapeutics, EIP farma, Esai, Janssen prevention center, Roche, Toyama, and Vivoryon. Sasha Bozeat and Frances‐Catherine Quevenco are paid employees of Roche Diagnostic Solutions. Article processing charges were paid by Roche Diagnostics International Ltd.

Figures

FIGURE 1
FIGURE 1
Tau positron emission tomography imaging (left set of orthogonal views) and amyloid imaging (right set of orthogonal views) were taken when Mr. T was aged 70 years. He had prior amyloid imaging at age 62 years (not pictured) together with cerebrospinal fluid sampling and both demonstrated amyloid positivity at least 10 years before his diagnosis of mild cognitive impairment at age 72
See this image and copyright information in PMC

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