医学新闻：脑脊液的一组生物标志可以诊断出老年痴呆症患者

In an article published in the Journal of the American Medical Association, Swedish researchers claim that an analysis of specific biomarkers in a cerebrospinal fluid sample can differentiate patients with Alzheimer’s disease from those with other types of dementia. The method, which is being studied by researchers at Sahlgrenska Academy, University of Gothenburg, may eventually permit earlier detection of Alzheimer’s disease.

Due to the similarity of the symptoms, differentiating patients with Alzheimer’s from those with other types of dementia, and patients with Parkinson’s disease from those with other motor disorders, is often difficult. But making a proper diagnosis is essential if proper treatment and medication are to commence at an early stage. The researchers are developing a new method to differentiate patients with Alzheimer’s disease or Parkinson’s disease by analyzing a cerebrospinal fluid sample. The study, conducted among 450 patients at Skåne University Hospital and Sahlgrenska University Hospital, involved testing five proteins that serve as biomarkers for the two diseases.

“Previous studies have shown that Alzheimer’s disease is associated with biochemical changes in specific proteins of the brain,” says researcher Annika Öhrfelt. “This study has found that the inclusion of a new protein can differentiate patients with Alzheimer’s disease from those with Lewy body dementia, Parkinson’s disease dementia, and other types of dementia. Additional studies are needed before the biomarkers can be used in clinical practice during the early stages of disease, but these results represent an important step along the way.” Read the study abstract.

[论文摘要]

Accuracy of a Panel of 5 Cerebrospinal Fluid Biomarkers in the Differential Diagnosis of Patients With Dementia and/or Parkinsonian Disorders

Sara Hall, MD; Annika Öhrfelt, PhD; Radu Constantinescu, MD; Ulf Andreasson, PhD; Yulia Surova, MD; Fredrik Bostrom, MD; Christer Nilsson, MD, PhD; Håkan Widner, MD, PhD; Hilde Decraemer; Katarina Nägga, MD, PhD; Lennart Minthon, MD, PhD; Elisabet Londos, MD, PhD; Eugeen Vanmechelen, PhD; Björn Holmberg, MD, PhD; Henrik Zetterberg, MD, PhD; Kaj Blennow, MD, PhD; Oskar Hansson, MD, PhD

Arch Neurol. 2012;():1-8. doi:10.1001/archneurol.2012.1654.

Objective To assess the ability of 5 cerebrospinal fluid (CSF) biomarkers to differentiate between common dementia and parkinsonian disorders.

Design A cross-sectional, clinic-based study.

Participants Cerebrospinal fluid samples (N = 453) were obtained from healthy individuals serving as controls and from patients with Parkinson disease (PD), PD with dementia (PDD), dementia with Lewy bodies (DLB), Alzheimer disease (AD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), or corticobasal degeneration (CBD).

Setting Neurology and memory disorder clinics.

Main Outcome Measures Cerebrospinal fluid biomarker levels in relation to clinical diagnosis.

Results Cerebrospinal fluid levels of α-synuclein were decreased in patients with PD, PDD, DLB, and MSA but increased in patients with AD. Cerebrospinal fluid levels of β-amyloid 1-42 were decreased in DLB and even further decreased in AD. Cerebrospinal fluid levels of total tau and hyperphosphorylated tau were increased in AD. Multivariate analysis revealed that these biomarkers could differentiate AD from DLB and PDD with an area under the curve of 0.90, with α-synuclein and total tau contributing most to the model. Cerebrospinal fluid levels of neurofilament light chain were substantially increased in atypical parkinsonian disorders (ie, PSP, MSA, and CBD), and multivariate analysis revealed that the level of neurofilament light chain alone could differentiate PD from atypical parkinsonian disorders, with an area under the curve of 0.93.

Conclusions Ascertainment of the α-synuclein level in CSF somewhat improves the differential diagnosis of AD vs DLB and PDD when combined with established AD biomarkers. The level of neurofilament light chain alone may differentiate PD from atypical parkinsonian disorders.