Amyloid peptides and tau markers in CSF
Cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD), such as β-amyloid 1-42 (Aβ1-42), total tau (tTau) and pTau181, have improved the management of patients with cognitive impairment. Although Aβ1-42 is considered a marker of amyloid pathology, a series of studies have shown that a decrease in CSF Aβ1-42 is not specific to AD and can also be found in other pathological situations, such as inflammatory diseases, prionopathies, amyloid angiopathy, or frontotemporal dementia. The Aβ1-42/Aβ1-40 ratio has proven to be very useful in this context, allowing detection of amyloid pathology and showing a better correlation with brain amyloid load detected in PET than Aβ1-42 alone. However, the concordance between CSF Aβ1-42 and the Aβ1-42/Aβ1-40 ratio remains to be evaluated, in order to answer the question of whether these two markers equally follow the same pathophysiological process.
What have we done in this study?
In the present work, we studied CSF Aβ1-42 and the Aβ1-42/Aβ1-40 ratio in the Sant Pau Initiative on Neurodegeneration (SPIN) cohort of participants (n=1791), with a variety of neurodegenerative disorders including patients with mild cognitive impairment or dementia and with either pathophysiological evidence of AD, frontotemporal lobar degeneration-related syndromes or probable dementia with Lewy Bodies. We also included CSF samples from cognitively normal participants from the SPIN cohort and from participants with Down syndrome from the DABNI study. We compared the concordance between the two measures in these different disease settings and investigated their association with other CSF biomarkers (tTau, pTau181, NfL) and with cognitive and functional progression.
Among the 1791 participants, the concordance between Aβ1-42 and Aβ1-42/Aβ1-40 was high and the Aβ1-42/Aβ1-40 ratio showed stronger correlation with tTau and pTau181 than Aβ1-42. Participants with low Aβ1-42/Aβ1-40 ratio had worse cognitive and functional prognosis (independently of their Aβ1-42 levels). Results were consistent across stages and diagnostic categories of patients.
Relevance of the study
Although Aβ1-42 and Aβ1-42/Aβ1-40 are considered markers of the same pathophysiological pathway, our findings provide evidence favoring the use of the Aβ1-42/Aβ1-40 ratio in clinical laboratories in the context of AD. This information is highly relevant for the implementation and interpretation of these markers in clinical routine.