Cerebrospinal Fluid Classical Biomarker Levels in Mixed vs. Pure A⁺T⁺ (A⁺T₁⁺) Alzheimer's Disease

Background: Alzheimer's disease (AD) may present with pure (typical or atypical) and mixed phenotypes, sometimes causing difficulties in (differential) diagnosis. In order to achieve a diagnostic accuracy as high as possible, the diagnosis of AD during life depends on various biomarkers, including the cerebrospinal fluid (CSF) biomarkers. Methods: Classical CSF AD biomarkers were determined in a total of 61 patients, classified as both beta amyloid- and tau-positive A⁺T⁺ (or A⁺T₁⁺ according to the recently revised Alzheimer Association criteria for diagnosis and staging of AD). Twenty one of these patients fulfilled the criteria for mixed AD (mixed with Lewy bodies, cerebrovascular disease, or normal pressure hydrocephalus), whilst 40 had pure AD. Results: Patients did not differ with respect to gender, education, disease duration, and cognitive status. After controlling for confounding factors, no difference was observed between mixed and pure AD groups in Aβ₄₂ or Aβ₄₂/Aβ₄₀ levels. Although by definition, patients of both groups had abnormal (increased) levels of phospho-tau₁₈₁, the mixed AD group presented with lower (less abnormal) levels of phospho-tau181 and total tau as compared to the pure group. Conclusions: In patients with AD of comparable cognitive status, mixed AD cases may present with lower levels of tau proteins and, if close to the cut-off values, diagnostic uncertainty may be increased.