Cerebrospinal Fluid Biomarkers in the Evaluation of Alzheimer Disease

Abstract

Alzheimer disease (AD),1 the most prevalent form of dementia in older adults, is a neurodegenerative disorder characterized by cerebral amyloid angiopathy, extracellular accumulation of amyloid β-protein (Aβ) in senile plaques, and intracellular accumulation of hyperphosphorylated τ proteins in neurofibrillary tangles in cortical and limbic brain regions. As life expectancy increases, the number of people suffering from dementia will grow considerably, causing an increasing burden on society, economy, and healthcare across the world. Until recently, a definitive diagnosis of AD could be made only after a postmortem examination of the patient. In living patients only a “probable AD” diagnosis is possible and is made on the basis of clinical features, the results of neurological and neuropsychological testing, and the exclusion of other dementias, in particular frontotemporal lobe degeneration, dementia with Lewy bodies, and vascular dementia. Accurate and early diagnosis is essential for appropriate support and treatment of dementia patients, because drugs are available for the symptomatic treatment of AD, and drugs that may slow or halt the progression of the disease are being developed, such as β-sheet breakers, inhibitors of the enzymes that produce Aβ from its precursor proteins (β- and γ-secretase), and immunotherapy targeted at Aβ(1). The clinical diagnostic criteria currently used for AD, the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association) criteria(2), were initially developed for research purposes. Results of several clinicopathological studies showed sensitivity of these criteria for AD to be as high as 93%, but their specificity was drastically lower(3). Clearly, the identification of AD biomarkers is an important step in improving the diagnostic accuracy for this disease(4). Analyses of various brain-specific proteins in cerebrospinal fluid (CSF), biomarkers with chemical composition that closely matches that of the brain, have …