Researchers sought to compare Aβ1–42 (β-amyloid 1–42) and the Aβ1–42/Aβ1–40 ratio in cerebrospinal fluid (CSF) in different neurodegenerative disorders and examined their link with other biomarkers [total tau (tTau), phosphorylated-tau-181 (pTau181), and neurofilament light] as well as with cognitive and functional progression. Based on the findings, Aβ1–42 and Aβ1–42/Aβ1–40 were considered markers of the same pathophysiological pathway, but the generated evidence favor the employment of the Aβ1–42/Aβ1–40 ratio in clinical laboratories in the context of Alzheimer disease (AD).

• Participants with diagnoses of AD, dementia with Lewy bodies, frontotemporal lobar degeneration-related syndromes, non-neurodegenerative conditions, or were cognitively normal, with CSF Aβ1–42 and Aβ1–42/Aβ1–40, were included and classified as “positive” or “negative” according to each marker.

• This study included 1,791 participants, in whom agreement between Aβ1–42 and Aβ1–42/Aβ1–40 was found to be 78.3%.

• The Aβ1–42/Aβ1–40 ratio demonstrated a stronger correlation with tTau and pTau181, in comparison to Aβ1–42, and an agreement with tTau and pTau181 of 73.1% and 77.1%, respectively.

• Higher tTau and pTau181 and worse cognitive and functional prognosis were observed in participants with a low Aβ1–42/Aβ1–40 ratio, irrespective of whether they were positive or negative for Aβ1–42.

• Findings remained consistent across stages, diagnostic categories, and use of different cutoffs.