Recent advances in cerebrospinal fluid biomarkers for the detection of preclinical Alzheimer's disease.
The concept of preclinical Alzheimer's disease has emerged to describe the long 'silent' phase of the disease when significant pathophysiological changes occur in the brain but clinical symptoms are not yet manifest. In this review, a summary of the recent advances in cerebrospinal fluid (CSF) biomarker-based diagnostics of preclinical Alzheimer's disease will be presented.



The association between core CSF biomarkers of Alzheimer's disease and between CSF and neuroimaging markers has been a major focus of various recently published studies in cognitively healthy individuals. Longitudinal results from several research groups suggest that CSF Aβ42 is altered early in preclinical Alzheimer's disease, even preceding changes on amyloid PET imaging. In line with the proposed NIA-AA criteria, elevated tau levels and/or Aβ/tau interactions appear to be a prerequisite for neurodegeneration and future cognitive decline. Novel candidate CSF markers, including markers of neuronal and synaptic injury as well as neuroinflammation, may complement CSF-based diagnostics in preclinical Alzheimer's disease.



Further longitudinal research is necessary to delineate the temporal changes of core and candidate CSF biomarkers in preclinical Alzheimer's disease and to investigate their association with established and emerging neuroimaging markers as well as with comorbidities and other risk factors for age-related cognitive decline.
aInstitute for Regenerative Medicine bClinic for Psychogeriatric Medicine cNeuroscience Center Zurich (ZNZ) dZurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
Luka
L
Kulic
Paul G
PG
Unschuld
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D006801:Humans; D059906:Neuroimaging; D049268:Positron-Emission Tomography
D016229:Amyloid beta-Peptides; D015415:Biomarkers