CSF Aβ40 and P-tau181 might differentiate atypical from typical AD phenotypes: preliminary evidence

Objectives. This study aimed at testing whether CSF levels of amyloid beta 42 (A beta 42), A beta 40, total tau and phosphorylated tau (P-tau181) individually contribute to the identification of atypical phenotypes among a retrospective cohort of probable AD patients diagnosed by means of the ratio between A beta 42 and A beta 40 (A beta 42/40). Methods. The retrospective study cohort comprised 50 probable AD patients diagnosed by means of the ratio between A beta 42 and A beta 40 (A beta 42/40) and for whom total tau and P-tau181 values were also available. Patients were clinically classified as typical, amnestic-predominant AD (N=39; 16 males; mean age: 73.4 +/- 7.6 years; mean disease duration: 27.4 +/- 24.7 months) or atypical phenotypes (N=11; 6 males; mean age: 70.2 +/- 6.5 years; mean disease duration: 35.5 +/- 24.9 months) - i.e., posterior cortical atrophy (PCA; N=4), logopenic-variant primary progressive aphasia (lvPPA; N=4) and behavioural-variant AD (bvAD; N=3). A logistic regression allowed to predict the occurrence of atypical vs. typical phenotypes based on age, sex, and A beta 42, A beta 40, total tau and P-tau181 levels. Results. Atypical and typical AD patients were comparable for A beta 42/40 values. Only A beta 40 and P-tau181 levels positively (p=.015) and negatively (p=.019) predicted the occurrence of atypical AD phenotypes, respectively. Classification precision was of 86%, yielding excellent specificity (94.9%), but poor sensitivity (54.5%). Conclusions. The present study delivers promising, albeit preliminary, evidence on the utility of A beta 40 and P-tau181 CSF biomarkers in differentiating atypical from typical A beta 42/40-confirmed AD phenotypes, prompting further research and confirmation on larger cohorts.

Automated summary

This study found that the levels of A beta 40 and P-tau181 in cerebrospinal fluid can predict the occurrence of atypical AD phenotypes. However, the sensitivity was poor, indicating the need for further research and validation.