Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in the Era of Disease-Modifying Treatments

Abstract

Correct in vivo diagnosis of Alzheimer's disease (AD) helps to avoid administration of disease-modifying treatments in non-AD patients, and allows the possible use of such treatments in clinically atypical AD patients. Cerebrospinal fluid (CSF) biomarkers offer a tool for AD diagnosis. A reduction in CSF β-amyloid (marker of amyloid plaque burden), although compatible with Alzheimer's pathological change, may also be observed in other dementing disorders, including vascular cognitive disorders due to subcortical small-vessel disease, dementia with Lewy bodies and normal-pressure hydrocephalus. Thus, for the diagnosis of AD, an abnormal result of CSF β-amyloid may not be sufficient, and an increase in phospho-tau (marker of tangle pathology) is also required in order to confirm AD diagnosis in patients with a typical amnestic presentation and reveal underlying AD in patients with atypical or mixed and diagnostically confusing clinical presentations.

Keywords: Alzheimer’s disease; aducanumab; anti-amyloid antibodies; beta amyloid; biomarkers; cerebrospinal fluid; phospho-tau.

Figure 1

Use of CSF classical biomarkers and the AT(N) classification system in everyday clinical practice, for the diagnosis of Alzheimer’s disease and Alzheimer’s pathological change. Other profiles are not compatible with Alzheimer’s continuum and are not shown.