Cerebrospinal Fluid Biomarkers of Alzheimer's Disease: Current Evidence and Future Perspectives.

Donovan A Mcgrowder,Chukwuemeka Nwokocha,Melisa Anderson-Cross,Lennox Anderson-Jackson,Kurt Vaz,Lowen Williams,Ruby Alexander-Lindo,Rory Thompson,Jabari Brown,Fabian Miller,Lyndon Latore,Cameil Wilson-Clarke

doi:10.3390/brainsci11020215

Abstract

Alzheimer’s disease is a progressive, clinically heterogeneous, and particularly complex neurodegenerative disease characterized by a decline in cognition. Over the last two decades, there has been significant growth in the investigation of cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease. This review presents current evidence from many clinical neurochemical studies, with findings that attest to the efficacy of existing core CSF biomarkers such as total tau, phosphorylated tau, and amyloid-β (Aβ42), which diagnose Alzheimer’s disease in the early and dementia stages of the disorder. The heterogeneity of the pathophysiology of the late-onset disease warrants the growth of the Alzheimer’s disease CSF biomarker toolbox; more biomarkers showing other aspects of the disease mechanism are needed. This review focuses on new biomarkers that track Alzheimer’s disease pathology, such as those that assess neuronal injury (VILIP-1 and neurofilament light), neuroinflammation (sTREM2, YKL-40, osteopontin, GFAP, progranulin, and MCP-1), synaptic dysfunction (SNAP-25 and GAP-43), vascular dysregulation (hFABP), as well as CSF α-synuclein levels and TDP-43 pathology. Some of these biomarkers are promising candidates as they are specific and predict future rates of cognitive decline. Findings from the combinations of subclasses of new Alzheimer’s disease biomarkers that improve their diagnostic efficacy in detecting associated pathological changes are also presented.

Highlights

Alzheimer’s DiseaseDementia defines a collection of symptoms due to acquired loss of cognition in numerous domains in such a manner that affects memory, occupational function, and thinking ability
This review presents current evidence from many clinical neurochemical studies on core and novel cerebrospinal fluid (CSF) biomarkers that assess all aspects of the pathophysiology of the disease
Aβ42 concentration discriminated between those with the disease and controls (Average ratio: 0.56, 95% CI: 0.55–0.58, p < 0.0001) Aβ42 concentration discriminated between mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) from stable MCI (Average ratio: 0.67)

Summary

Introduction

Dementia defines a collection of symptoms due to acquired loss of cognition in numerous domains in such a manner that affects memory, occupational function, and thinking ability. The impairment in cognition significantly interferes with an individual’s ability to maintain normal daily activity and live a fully autonomous and purposeful life [1]. Alzheimer’s disease is the most common cause of dementia, encompassing 60–80% of cases. It has an estimated prevalence of over 40 million individuals worldwide and is reported to be the sixth leading cause of death [2]. In the United States of America, an estimated prevalence of 3% has been reported for persons 65–74 years of age, 17% for 75–84 years of age, and 32% for those individuals 85 years and older [3]

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