Decreased β-Amyloid_1-42and Increased Tau Levels in Cerebrospinal Fluid of Patients With Alzheimer Disease

Abstract

HILE THE EXACT BIOLOGIcal cascade associated with Alzheimer disease (AD) is only partially understood, many potential biomarkers of this disease process are known. 1 Two of the most obvious candidates are ␤-amyloid 1-42 and tau proteins, as they are intimately related to the pathognomonic features of amyloid plaques and neurofibrillary tangles in the AD brain. 2,3 Multiple previous studies have reported decreases in cerebrospinal fluid (CSF) measures of ␤-amyloid. 4-7 Similarly, CSF measures of tau have routinely showed considerable elevations of this peptide in AD cases worldwide. 7-12 Some authors have reported that these 2 measures alone can accurately differentiate clinically diagnosed AD cases from controls more than 85% of the time. 7,13 Studies of CSF in AD patients have used widely varying methods and nomenclature for assessing and describ-Author Affiliations are listed at the end of this article.

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

“…The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of ␤-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson's disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia.…”

“…A moderate to marked decrease in CSF A␤42 in AD to about 50% of control levels has been found using the majority of these methods (Table 1). 35,39,[41][42][43][44][45]47,48 An increase in CSF A␤42 in AD was found in one study. 46 This finding may be attributable to methodological differences (e.g., assay specificity for aggregated or truncated A␤ variants).…”

“…However, in a large study on 131 AD cases in which the diagnosis was confirmed at autopsy in 31 cases, the performance of CSF T-tau and A␤42 was similar in both groups. 43 Since CSF T-tau reflects neuronal and axonal degeneration, it is not specific for AD; high CSF T-tau levels will be found in all CNS disorders with neuronal degeneration or damage. The highest levels are found in acute stroke 18 and in CJD.…”

Ocular Biomarkers for Early Detection of Alzheimer's Disease

“…CSF biomarkers have proven to be the most accurate of the biomarkers investigated to date, with AD being shown to be associated with decreased Aβ42 levels and increased tau levels in the CSF [33]. However the latter procedure is invasive and patient compliance is anticipated to be low.…”

Trabalho de consenso de força-tarefa da WFSBP sobre marcadores biológicos das demências: contribuição da análise do LCR e do sangue para o diagnóstico precoce e diferencial das demências

“…Por meio de uma metanálise, Sunderland et al (2003) examinaram os achados de 17 artigos sobre Aβ42 e 34 artigos sobre tau no LCR de pacientes com DA. Todos os estudos incluídos nessa metanálise relataram aumento de tau total no LCR na DA.…”