Researchers from Amsterdam Neuroscience, in collaboration with the Born-Bunge Institute of the University of Antwerp, characterized the ability for Alzheimer’s disease cerebrospinal fluid (CSF) biomarkers to reflect neuropathological changes later in the disease course. They concluded that the CSF biomarkers may not be well suited for staging or monitoring AD pathology as it progresses through later stages. Their findings were published in the scientific journal Brain.

Alzheimer’s disease (AD) CSF biomarkers Amyloid-Beta-42, total tau protein (T-tau) and P-tau improve clinical diagnosis of AD. These biomarkers are considered to reflect a biomarker of AD pathology, each a different aspect thereof. The association between the CSF biomarkers and neuropathology may vary through different stages of the disease. This modulates the ability of the biomarkers to stage or monitor neuropathology as the disease progress. Therefore, this multicenter study investigated how AD CSF biomarkers measured in mid- to late- AD reflect the end-stage neuropathology.

In the same individual, they quantitatively looked at the relation between antemortem CSF biomarkers and postmortem neuropathological changes reported. They did not find an association between Amyloid-Beta-42 and AD neuropathological change profile. However, they did observe an association of P-tau and T-tau with AD neuropathological change profile. The P-tau CSF biomarker was associated with all three individual Montine scores. This association became stronger and more significant when the CSF was retrieved closer to death. T-tau was also associated with all three Montine scores, however, this was only in individuals with longer intervals between lumbar puncture and death.

Their data suggest that P-tau and T-tau reach a plateau level during the disease course, similarly to Amyloid-Beta-42. Because of this, the potential of tau biomarkers to monitor AD pathology as the disease progresses is reduced. This data shows that CSF biomarkers, functioning well for clinical diagnosis of early AD, may not be well suited for staging or monitoring the progress of AD through later stages.

Read the publication in Brain: Associating Alzheimer’s disease pathology with its cerebrospinal fluid biomarkers