Real-world clinical profile of individuals with cerebrospinal fluid Aβ – /pTau181 +

Abstract

Background

Cerebrospinal fluid (CSF) pTau181 is used to support Alzheimer's disease (AD) diagnosis but can also rise in amyloid-negative individuals. This CSF profile (Aβ⁻/pTau181⁺) lies outside the AD continuum and complicates real-world etiologic diagnosis of neurocognitive disorders.

Objective

To determine the prevalence and clinical phenotype associated with the Aβ⁻/pTau181⁺ CSF biomarker profile in a real-world memory clinic population.

Methods

We screened the Mount Sinai Hospital database (2015–2024) for patients who underwent ADmark CSF biomarker testing. An Aβ⁻/pTau181⁺ group was classified using assay cutoffs (Amyloid-Total-Tau Index>1.2, pTau181 > 54 pg/mL) and compared to an Aβ⁺ group (Amyloid-Total-Tau Index<0.8) matched for pTau181 and total-Tau. Clinical variables were extracted via chart review, limited to notes preceding CSF and blinded to CSF results.

Results

The Aβ⁻/pTau181⁺ group included 25 individuals (10.1% of the cohort) and had equally impaired cognition but fewer episodic memory complaints. Diagnosis was more often Lewy body or frontotemporal dementia. On neuroimaging, Aβ⁻/pTau181⁺ exhibited less white matter hyperintensity burden and temporoparietal atrophy.

Conclusions

CSF Aβ⁻/pTau181⁺ is frequent in real-world evaluations of cognitive impairment and presents with fewer AD phenotypic features. Further research is required to clarify Aβ⁻/pTau181⁺ underlying biology and clinical trajectory.