Alzheimer Disease Biomarkers in Clinical Practice: A Blood-Based Diagnostic Revolution

Abstract

An estimated 6.1 million Americans live with cognitive impairment-a number that is expected to triple by 2050. Alzheimer disease (AD) is the most common cause of impairment. The development of blood-based biomarkers capable of detecting pathological changes of AD in living patients has the potential to revolutionize the diagnostic approach to cognitive impairment by enabling screening for AD using accessible, non-invasive measures of amyloid and tau neuropathology, with accuracy that increasingly approaches that seen with "gold standard" positron emission tomography and cerebrospinal fluid measures. Demand for biomarker testing is expected to intensify with the emergence of effective treatments for AD and related dementias. Clinicians in all fields must prepare to meet this demand. Primary care practitioners are well positioned to support dementia diagnosis and management, including the application and interpretation of biomarkers. This article reviews the current uses of AD biomarkers and the potential applications of emerging blood-based AD biomarkers in clinical practice.

Keywords: Alzheimer disease; amyloid; blood biomarkers; dementia; mild cognitive impairment; screening; tau.

Figure 1.

Diagnostic challenges in Alzheimer disease. The accurate diagnosis of Alzheimer disease requires a detailed history, physical examination and testing to rule-in Alzheimer disease and rule-out other causes of cognitive impairment. The initial workup for cognitive complaints typically includes a standardized mental status assessment (Montreal Cognitive Assessment, Mini-Mental Status Examination), screening for B12 deficiency and thyroid dysfunction, and often neuroimaging (brain magnetic resonance imaging or computerized tomography). Limited time and resources, variability in the clinical presentation and inefficacies in screening challenge accurate and efficient recognition of cognitive impairment in clinical practice and contribute to underdiagnoses and misdiagnoses of symptomatic Alzheimer disease.

Figure 2.

The relationship between Alzheimer disease (AD) pathology and cognitive function across the lifespan. Accrual of AD neuropathology begins decades before the emergence of cognitive complaints, identified as the “preclinical” (or presymptomatic) period (A). Declines in cognitive function attributable to AD neuropathology herald the onset of “clinical” (or symptomatic) AD (B), a period that commonly lasts between 8 and 12 years (C). The protracted “preclinical” period presents an ideal time during which treatments could be provided to at-risk individuals to prevent or reverse the accrual of AD neuropathology and delay the onset or progression of clinical AD.