Different cutoffs definitions to evaluate the concordance between CSF Ab42 and Ab42/Ab40 across neurodegenerative diseases

Background Cerebrospinal fluid (CSF) Aβ1-42 and the Aβ1-42/Aβ1-40 ratio are markers of amyloid pathology. We aimed to compare their agreement in different neurodegenerative disorders applying cutoffs. Method included 1564 participants from Sant Pau Initiative on Neurodegeneration (SPIN), with AD, dementia Lewy bodies (DLB), frontotemporal lobar degeneration-related syndromes (FTLD), cognitively impaired but non-neurodegenerative conditions (others), normal individuals (CN). Cutoffs were defined as one-sided 97.5%, 95% 90% (Q97.5%, Q95% Q90%, respectively) quantiles values a middle-aged population. These cutoffs for (617 pg/mL, 637 pg/mL 732 (0.060, 0.070 0.082, used classify all “positive” or “negative” according each marker. compared concordance between groups through X2 test correlations Spearman test. Result Correlation CSF was strong (0.71, p<0.001) whole cohort, DLB others (0.69 0.64, respectively, both p<0.0001); correlation weak FTLD CN (0.33, 0.52 0.51, p<0.0001). Using Q97.5%, Q90% cutoffs, had an overall 76.6%, 78.3% 82.9%, respectively sample. Both measures (« negative ») 46.1%, 41.6% 35.8%, abnormal positive 30.5%, 36.7% 47.1% participants, respectively. Within diagnostic category, ranged 64% (AD) 91.5% (CN) using 69.6% 88.7% 78.9% (DLB) 85.9% Q90%. Regardless cutoff definition, most discordant cases AD due low ratio, while more frequently ratio. Conclusion Although may reflect same pathophysiological pathway, depends definition. Our results confirm that parameters show medium high concordance, case discordance, positivity is associated non-AD dementias, independently used.