CSF Aβ40 and P-Tau181 Might Differentiate Atypical from Typical AD Phenotypes: Preliminary Evidence

Abstract

Objectives: This study aimed at testing whether CSF levels of amyloid β₄₂ (Aβ₄₂), Aβ₄₀, total tau, and phosphorylated tau (P-tau₁₈₁) individually contribute to the identification of atypical phenotypes among a retrospective cohort of probable Alzheimer’s disease (AD) patients diagnosed by means of the ratio between Aβ₄₂ and Aβ₄₀ (Aβ_42/40). Methods: The retrospective study cohort comprised 50 probable AD patients diagnosed by means of the ratio between Aβ₄₂ and Aβ₄₀ (Aβ_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 (N = 4), logopenic-variant primary progressive aphasia (N = 4), and behavioural variant AD (N = 3). A logistic regression allowed predicting the occurrence of atypical versus typical phenotypes based on age, sex, and Aβ₄₂, Aβ₄₀, total tau, and P-tau₁₈₁ levels. Results: Atypical and typical AD patients were comparable for Aβ_42/40 values. Only Aβ₄₀ and P-tau₁₈₁ levels positively (p = 0.015) and negatively (p = 0.019) 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 Aβ₄₀ and P-tau₁₈₁ CSF biomarkers in differentiating atypical from typical Aβ_42/40-confirmed AD phenotypes, prompting further research and confirmation on larger cohorts.