Cerebrospinal fluid markers detect Alzheimer's disease in nonamnestic dementia

Abstract

Introduction: The accuracy of cerebrospinal fluid (CSF) biomarkers for detecting Alzheimer's disease (AD) pathology has not been fully validated in autopsied nonamnestic dementias.

Methods: We retrospectively evaluated CSF amyloid β 1-42, phosphorylated-tau, and amyloid-tau index as predictors of Alzheimer pathology in patients with primary progressive aphasia, frontotemporal dementia, and progressive supranuclear palsy.

Results: Nineteen nonamnestic autopsied cases with relevant CSF values were included. At autopsy, nine had AD and 10 had non-AD pathologies. All six patients whose combined CSF phosphorylated-tau and amyloid β levels were "consistent with AD" had postmortem Alzheimer pathology. The two patients whose biomarker values were "not consistent with AD" had non-AD pathologies. The CSF values of the remaining eight non-AD cases were in conflicting or borderline ranges.

Discussion: CSF biomarkers reliably identified Alzheimer pathology in nonamnestic dementias and may be useful as a screening measure for inclusion of nonamnestic cases into Alzheimer's trials.

Keywords: Atypical Alzheimer's disease; Behavioral variant frontotemporal dementia; Neuropathology; Primary progressive aphasia; Progressive supranuclear palsy.

Fig. 1

The amyloid-tau index (ATI) versus phosphorylated-tau (p-tau) in picograms per milliliter for all patients with nonamnestic dementia syndromes and autopsy-confirmed pathologies. The upper left quadrant contains values not consistent with AD, whereas the lower right quadrant represents values consistent with AD. The upper right and lower left quadrants represent values with conflicting information. The dashed lines surround the regions considered to lie within a borderline zone and are bound by ATI ranging from 0.8 to 1.2 and p-tau of 54 to 68 pg/mL. Black symbols represent AD pathology and white symbols represent nonAD pathology. Triangles denote FTD as clinical diagnosis, circles denote PPA as the clinical diagnosis, and squares denote PSP as a clinical diagnosis. Abbreviations: AD, Alzheimer’s disease; FTD, frontotemporal dementia; PPA, primary progressive aphasia; PSP, progressive supranuclear palsy. *Note these are two data points that are very close together, both are white triangles representing FTD-nonAD.